Downloaded from www.sciencemag.org on June 18, 2015
PERSPECTIVES
Although gray wolf (Canis lupus) populations are recovering in parts of Europe and North America, wolves continue to be killed in attempts to protect livestock and threatened species such as caribou.
CONSERVATION
When the hunter becomes the hunted By Rosie Woodroffe1 and Stephen M. Redpath2
H
istorically, wild predators were overwhelmingly viewed as threats to livestock, wild “game,” and public health. Over time, public perceptions have broadened to include recognition of predators’ intrinsic value and their role in structuring ecosystems. Nowhere are these changing perceptions better illustrated than in Yellowstone National Park, where the U.S. government deliberately eliminated wolves in the 1920s, only to actively restore them in the 1990s. Large carnivores are now recovering across much of North America and Europe but declining elsewhere (1, 2).
1
Institute of Zoology, Regent’s Park, London NW1 4RY, UK. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK. E-mail: [email protected]; [email protected] 2
1312
Predator control, once widely accepted by the public, has become a source of intense social conflict (3, 4). Robust scientific evidence and broad stakeholder involvement are crucial for effective management of predator populations. Randomized controlled experiments have repeatedly shown that predator control can bolster populations of prey species, including many of conservation concern (5, 6). However, the complexity of ecological systems means that predator control does not invariably benefit wild prey. In some ecosystems, factors such as habitat loss or weather conditions influence prey numbers more strongly than does predation. Suppressing the populations of one predator species may cause other predators to increase in number, leaving prey to face unchanged or even heightened predation rates. For example, Ellis-Felege et al. have shown in an experimen-
tal study that predator control efforts reduce mammalian predation on bobwhite quail nests in the southeastern United States, but these benefits are offset by increased predation from snakes (7). Similarly, pronghorn (which are preyed on by coyotes but seldom by wolves) appear to have declined in response to the extirpation of wolves, which caused a dramatic expansion of coyotes across North America (8). Predator control is thus not invariably beneficial, and decisions about its use need to be informed by case-specific evidence. The best evidence comes from controlled experimental studies, which have been widely used to understand the effects of predator control on wild prey. However, decisions about controlling predators to protect livestock or manage disease have often been based on much weaker evidence. For example, despite the enormous effort invested in controlsciencemag.org SCIENCE
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
PHOTO: DENNIS DONOHUE/THINKSTOCK
Effective predator management relies on social acceptability as well as scientific evidence
INSIGHTS
ling populations of red foxes, coyotes, and wolves, we are not aware of any randomized experiments that investigate whether such control reduces livestock predation as intended. This is problematic because it is often difficult to disentangle cause and effect in observational studies. The ability of experimentation to improve evidence in such cases is illustrated by the management of bovine tuberculosis in Britain. The role of European badgers in transmitting tuberculosis to cattle was recognized in the 1970s, but decades of badger culling failed to prevent the infection from spreading across Britain. A randomized controlled trial revealed that culling consistently increased infection rates in badgers, spreading the disease in space and, under some circumstances, elevating disease risks for cattle (9). This failure of predator control to effect disease control is linked to the social behavior of these territorial animals. When badgers are killed in one area, other badgers migrate into the newly available territory. The resulting social instability is thought to increase opportunities for disease transmission (9). A similar behavioral response was seen among red fox populations culled across Europe in the 1970s to control rabies (10). Such fox control efforts were gradually abandoned as practical experience showed fox vaccination to be far more effective (10). Predator control conducted for a specific purpose often has broader consequences, which may be as unwelcome as they are unintended. Control or elimination of large carnivores, mainly to reduce livestock depredation, has been linked to increased deer numbers across Europe and North America. These larger deer populations damage forests and crops, reduce road safety, and have cascading effects on ecosystems (11). Extirpating wolves across much of North America stopped wolves from killing sheep, but introduced a new sheep predator as coyotes spread across the continent. Likewise, culling badgers for disease control purposes in the United Kingdom doubled the numbers of another farm pest, the red fox (12). The potential for predator control to cause unwanted side-effects should be considered seriously in environmental impact assessments and other policy decisions. In deciding how and whether to manage predation, it is also important to bear in mind that the need for predator control is itself often a consequence of human action. For example, in Patagonia, guanacos are kept in low numbers by their natural predator, the puma. Normally predator numbers would fall as their prey decline, but pumas are sustained by sheep, deer, and
hares introduced by people, allowing them to maintain high predation pressure on the few remaining guanacos (13). Similarly, Canadian oil developments have opened up the boreal forest, allowing deer numbers to increase and improving access to the forest for wolves. As a consequence, endangered woodland caribou face unsustainable predation, prompting the Canadian state governments to shoot, trap, and poison wolves in an attempt to protect the caribou (14). More generally, many studies have found predation on birds’ nests is higher where human activities have fragmented natural habitat. Predator control efforts aimed at conserving threatened prey may need to be maintained
decision-makers might prioritize economic gains. They might then consider the need for wolf control (or indeed the loss of woodland caribou) a small price to pay for the prosperity achieved through oil exploitation. The caribou inhabiting Canada’s boreal forest have come to resemble the partridges struggling to survive in England’s wheat fields; both may remain reliant on predator control unless or until society is willing to restore their natural habitat. Robust scientific evidence alone is not sufficient to manage predators effectively; social acceptability is equally important. Pragmatic conservationists have long recognized that allowing some predator control—whether or not it achieves its stated aims—can help to build tolerance among land managers who might otherwise block conservation efforts (3). Unfortunately, such compromise is not always effective. For example, small-scale culling of badgers on and around farms experiencing tuberculosis would be more socially acceptable than widespread badger control. However, such localized culling consistently increases cattle tuberculosis (9). Policy-makers are thus faced with a stark choice between near-elimination of a native carnivore (unpopular with the public and potentially unlawful) or no badger control at all (unpopular with farmers). The British government’s decision to pursue large-scale badger culling became an issue in the recent national election, and culls have
PHOTO: SETH JACKSON/ZSL INSTITUTE OF ZOOLOGY
“…the need for predator control is itself often a consequence of human action.” in perpetuity unless conservation seeks to restore ecosystem functioning. Decisions about how to manage predation in such human-altered systems are driven as much by the priorities of decision-makers as by rigorous scientific evidence. For example, decision-makers responding to woodland caribou declines might choose to prioritize biodiversity conservation. They would then prefer habitat restoration over wolf control, because this approach preserves predation as an ecosystem process. Alternatively,
European badgers (Meles meles) transmit tuberculosis to cattle, but efforts to control tuberculosis by culling badgers have not been effective because they do not take their social behavior into account.
SCIENCE sciencemag.org
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
1313
INSIGHTS | P E R S P E C T I V E S
been repeatedly delayed by legal challenges. Controversy about predator management can lead to intense social discord, which may undermine management decisions. For example, in Britain conservation efforts for hen harriers have been hampered by persistent illegal killing, while attempts to control cattle tuberculosis by killing badgers have been disrupted by dedicated protestors. Where social conflict is intense, scientific evidence is often used selectively, contested, or dismissed. In such situations, involving stakeholders in the design, implementation, and interpretation of experimental studies may help to build trust and improve social learning. For example, controversy over grizzly bear management in Banff National Park, Canada, was successfully resolved by engaging stakeholders in a problem-solving group, which shared responsibility for interpreting scientific evidence and making management decisions (15). Similar approaches might benefit the management of ecologically complex and socially divisive issues such as tuberculosis in badgers, wolf predation on caribou, and hen harrier predation on grouse (4). The challenge, especially in more intense social conflicts over predators, is that polarized views may prevent parties from engaging with the process at all. If policy-makers, scientists, and stakeholders from all sides can show leadership in overcoming this challenge, predator management might become more evidence-based, as well as more responsive to changing social perspectives. ■ REFERENCES
1. G. Chapron et al., Science 346, 1517 (2014). 2. W. J. Ripple et al., Science 343, 151 (2014). 3. R. Woodroffe, S. Thirgood, A. R. Rabinowitz, People and Wildlife: Conflict or Coexistence? (Cambridge Univ. Press, Cambridge, 2005). 4. S. M. Redpath, R. J. Gutiérrez, K. A. Wood, J. C. Young, Conflicts in Conservation: Navigating Towards Solutions (Cambridge Univ. Press, Cambridge, 2015). 5. A. R. Holt, Z. G. Davies, C. Tyler, S. Staddon, PLOS ONE 3, 8 (2008). 6. R. K. Smith, A. S. Pullin, G. B. Stewart, W. J. Sutherland, Conserv. Biol. 24, 820 (2010). 7. S. N. Ellis-Felege, M. J. Conroy, W. E. Palmer, J. P. Carroll, J. Appl. Ecol. 49, 661 (2012). 8. K. M. Berger, E. M. Gese, J. Berger, Ecology 89, 818 (2008). 9. J. Bourne et al., Bovine TB: The Scientific Evidence (Defra, http://archive.defra.gov.uk/foodfarm/farmanimal/ diseases/atoz/tb/isg/report/final_report.pdf, London, 2007). 10. D. W. Macdonald, Rabies and Wildlife–a Biologist’s Perspective (Oxford Univ. Press, Oxford, 1980). 11. S. D. Cote, T. P. Rooney, J. P. Tremblay, C. Dussault, D. M. Waller, Annu. Rev. Ecol. Evol. Syst. 35, 113 (2004). 12. I. D. Trewby et al., Biol. Lett. 4, 170 (2008). 13. A. J. Novaro, R. S. Walker, in Large Carnivores and the Conservation of Biodiversity, J. C. Ray, K. H. Redford, R. S. Steneck, J. Berger, Eds. (Island Press, Washington, DC, 2005), pp. 268–288. 14. D. Hervieux, M. Hebblewhite, D. Stepnisky, M. Bacon, S. Boutin, Can. J. Zool. 92, 1029 (2014). 15. M. L. Gibeau, Wildl. Prof. 6, 62 (2012).
10.1126/science.aaa8465
1314
CELL BIOLOGY
An ESCRT to seal the envelope Cellular machinery that remodels different lipid bilayers also closes the nuclear membrane By Wesley I. Sundquist1 and Katharine S. Ullman2
M
etazoan cells divide by “open” mitosis, in which disassembly of the nucleus allows microtubules of the mitotic spindle to access kinetochores, proteinaceous structures that associate with specialized regions of chromosomes called centromeres. Duplicated chromosomes align on the spindle, and as they segregate toward opposite ends of the dividing cell, nuclear membrane reassembly initiates (1). This requires recruiting membrane, reconstituting nuclear pores, and severing microtubule connections between chromosomes and the spindle organizing centers (centrosomes). The nuclear envelope must seal to reestablish proper separation of the genome from the cytoplasm, but just how the nuclear membrane closes and overcomes the physical roadblocks presented by spindle microtubules has been unclear. Recent studies (2, 3) now demonstrate that the endosomal sorting complex required for transport (ESCRT) membrane fission machinery orchestrates this mysterious process. Membrane fission, the process by which a continuous lipid bilayer separates into two discontinuous bilayers, occurs constantly as cells remodel their membranes. It can occur with two distinct topologies: one in which the juxtaposing membranes are drawn together at a cytoplasm-filled neck, and another in which they are drawn together at a cytoplasm-surrounded neck. Many familiar processes, such as endocytic vesicle formation, correspond to the latter topology, where the cytoplasmic protein dynamin encircles the constricting neck and “pushes” the membranes toward the fission point. By contrast, ESCRT protein assemblies work from inside membrane necks to “pull” the constricting membranes toward themselves (4, 5). Two keys to this activity are the ability of ESCRT-III family members to form spiraling filaments that can draw membranes toward the fission point (6–8), and the ability of vacuolar protein sorting 4 (VPS4) to remodel these filaments and thereby provide the power for membrane fission (4, 5). ESCRT-III subunits also recruit relevant proteins through their exposed terminal
tails. Because of its unique activity, the ESCRT machinery is used in a variety of different membrane remodeling processes, including intraluminal vesicle formation in the late endosome, enveloped virus budding, wound healing, and the final stage of daughter cell physical separation (cytokinetic abscission) during cell division (4, 5, 9, 10). The studies by Vietri et al. (2) and Olmos et al. (3) reveal that the ESCRT pathway also reseals the nuclear envelope during late anaphase-early telophase stages of the cell division cycle (see the figure). The breakthrough was made possible, in part, because the investigators studied specific sites in the nuclear envelope at relevant times by combining live-cell imaging of transient events and higher-resolution
“Mechanisms that reseal the nuclear envelope have been unclear, but a role for ESCRT machinery should now be considered.” microscopic techniques, including structured illumination microscopy and correlative light and electron microscopy. The studies report that ESCRT-III and VPS4 assemble briefly at fenestrations in the growing nuclear envelope, and that assembly of core ESCRT-III subunits occurs in a canonical fashion, with component charged multivesicular body protein 4 (CHMP4), CHMP3, and CHMP2 proteins recruited sequentially (5). In the absence of successful ESCRT assembly, postmitotic nuclear envelopes have unsealed holes and are functionally “leaky.” Although the two studies agree on the essential role of ESCRT machinery in closing nuclear fenestrations, each also adds unique insights into this process. ESCRT-III proteins function at many different mem1
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA. 2Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5650, USA. E-mail: [email protected]; [email protected]
sciencemag.org SCIENCE
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
When the hunter becomes the hunted Rosie Woodroffe and Stephen M. Redpath Science 348, 1312 (2015); DOI: 10.1126/science.aaa8465
This copy is for your personal, non-commercial use only.
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here.
The following resources related to this article are available online at www.sciencemag.org (this information is current as of June 18, 2015 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6241/1312.full.html This article cites 10 articles, 2 of which can be accessed free: http://www.sciencemag.org/content/348/6241/1312.full.html#ref-list-1 This article appears in the following subject collections: Ecology http://www.sciencemag.org/cgi/collection/ecology
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on June 18, 2015
Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here.
PERSPECTIVES
Although gray wolf (Canis lupus) populations are recovering in parts of Europe and North America, wolves continue to be killed in attempts to protect livestock and threatened species such as caribou.
CONSERVATION
When the hunter becomes the hunted By Rosie Woodroffe1 and Stephen M. Redpath2
H
istorically, wild predators were overwhelmingly viewed as threats to livestock, wild “game,” and public health. Over time, public perceptions have broadened to include recognition of predators’ intrinsic value and their role in structuring ecosystems. Nowhere are these changing perceptions better illustrated than in Yellowstone National Park, where the U.S. government deliberately eliminated wolves in the 1920s, only to actively restore them in the 1990s. Large carnivores are now recovering across much of North America and Europe but declining elsewhere (1, 2).
1
Institute of Zoology, Regent’s Park, London NW1 4RY, UK. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK. E-mail: [email protected]; [email protected] 2
1312
Predator control, once widely accepted by the public, has become a source of intense social conflict (3, 4). Robust scientific evidence and broad stakeholder involvement are crucial for effective management of predator populations. Randomized controlled experiments have repeatedly shown that predator control can bolster populations of prey species, including many of conservation concern (5, 6). However, the complexity of ecological systems means that predator control does not invariably benefit wild prey. In some ecosystems, factors such as habitat loss or weather conditions influence prey numbers more strongly than does predation. Suppressing the populations of one predator species may cause other predators to increase in number, leaving prey to face unchanged or even heightened predation rates. For example, Ellis-Felege et al. have shown in an experimen-
tal study that predator control efforts reduce mammalian predation on bobwhite quail nests in the southeastern United States, but these benefits are offset by increased predation from snakes (7). Similarly, pronghorn (which are preyed on by coyotes but seldom by wolves) appear to have declined in response to the extirpation of wolves, which caused a dramatic expansion of coyotes across North America (8). Predator control is thus not invariably beneficial, and decisions about its use need to be informed by case-specific evidence. The best evidence comes from controlled experimental studies, which have been widely used to understand the effects of predator control on wild prey. However, decisions about controlling predators to protect livestock or manage disease have often been based on much weaker evidence. For example, despite the enormous effort invested in controlsciencemag.org SCIENCE
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
PHOTO: DENNIS DONOHUE/THINKSTOCK
Effective predator management relies on social acceptability as well as scientific evidence
INSIGHTS
ling populations of red foxes, coyotes, and wolves, we are not aware of any randomized experiments that investigate whether such control reduces livestock predation as intended. This is problematic because it is often difficult to disentangle cause and effect in observational studies. The ability of experimentation to improve evidence in such cases is illustrated by the management of bovine tuberculosis in Britain. The role of European badgers in transmitting tuberculosis to cattle was recognized in the 1970s, but decades of badger culling failed to prevent the infection from spreading across Britain. A randomized controlled trial revealed that culling consistently increased infection rates in badgers, spreading the disease in space and, under some circumstances, elevating disease risks for cattle (9). This failure of predator control to effect disease control is linked to the social behavior of these territorial animals. When badgers are killed in one area, other badgers migrate into the newly available territory. The resulting social instability is thought to increase opportunities for disease transmission (9). A similar behavioral response was seen among red fox populations culled across Europe in the 1970s to control rabies (10). Such fox control efforts were gradually abandoned as practical experience showed fox vaccination to be far more effective (10). Predator control conducted for a specific purpose often has broader consequences, which may be as unwelcome as they are unintended. Control or elimination of large carnivores, mainly to reduce livestock depredation, has been linked to increased deer numbers across Europe and North America. These larger deer populations damage forests and crops, reduce road safety, and have cascading effects on ecosystems (11). Extirpating wolves across much of North America stopped wolves from killing sheep, but introduced a new sheep predator as coyotes spread across the continent. Likewise, culling badgers for disease control purposes in the United Kingdom doubled the numbers of another farm pest, the red fox (12). The potential for predator control to cause unwanted side-effects should be considered seriously in environmental impact assessments and other policy decisions. In deciding how and whether to manage predation, it is also important to bear in mind that the need for predator control is itself often a consequence of human action. For example, in Patagonia, guanacos are kept in low numbers by their natural predator, the puma. Normally predator numbers would fall as their prey decline, but pumas are sustained by sheep, deer, and
hares introduced by people, allowing them to maintain high predation pressure on the few remaining guanacos (13). Similarly, Canadian oil developments have opened up the boreal forest, allowing deer numbers to increase and improving access to the forest for wolves. As a consequence, endangered woodland caribou face unsustainable predation, prompting the Canadian state governments to shoot, trap, and poison wolves in an attempt to protect the caribou (14). More generally, many studies have found predation on birds’ nests is higher where human activities have fragmented natural habitat. Predator control efforts aimed at conserving threatened prey may need to be maintained
decision-makers might prioritize economic gains. They might then consider the need for wolf control (or indeed the loss of woodland caribou) a small price to pay for the prosperity achieved through oil exploitation. The caribou inhabiting Canada’s boreal forest have come to resemble the partridges struggling to survive in England’s wheat fields; both may remain reliant on predator control unless or until society is willing to restore their natural habitat. Robust scientific evidence alone is not sufficient to manage predators effectively; social acceptability is equally important. Pragmatic conservationists have long recognized that allowing some predator control—whether or not it achieves its stated aims—can help to build tolerance among land managers who might otherwise block conservation efforts (3). Unfortunately, such compromise is not always effective. For example, small-scale culling of badgers on and around farms experiencing tuberculosis would be more socially acceptable than widespread badger control. However, such localized culling consistently increases cattle tuberculosis (9). Policy-makers are thus faced with a stark choice between near-elimination of a native carnivore (unpopular with the public and potentially unlawful) or no badger control at all (unpopular with farmers). The British government’s decision to pursue large-scale badger culling became an issue in the recent national election, and culls have
PHOTO: SETH JACKSON/ZSL INSTITUTE OF ZOOLOGY
“…the need for predator control is itself often a consequence of human action.” in perpetuity unless conservation seeks to restore ecosystem functioning. Decisions about how to manage predation in such human-altered systems are driven as much by the priorities of decision-makers as by rigorous scientific evidence. For example, decision-makers responding to woodland caribou declines might choose to prioritize biodiversity conservation. They would then prefer habitat restoration over wolf control, because this approach preserves predation as an ecosystem process. Alternatively,
European badgers (Meles meles) transmit tuberculosis to cattle, but efforts to control tuberculosis by culling badgers have not been effective because they do not take their social behavior into account.
SCIENCE sciencemag.org
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
1313
INSIGHTS | P E R S P E C T I V E S
been repeatedly delayed by legal challenges. Controversy about predator management can lead to intense social discord, which may undermine management decisions. For example, in Britain conservation efforts for hen harriers have been hampered by persistent illegal killing, while attempts to control cattle tuberculosis by killing badgers have been disrupted by dedicated protestors. Where social conflict is intense, scientific evidence is often used selectively, contested, or dismissed. In such situations, involving stakeholders in the design, implementation, and interpretation of experimental studies may help to build trust and improve social learning. For example, controversy over grizzly bear management in Banff National Park, Canada, was successfully resolved by engaging stakeholders in a problem-solving group, which shared responsibility for interpreting scientific evidence and making management decisions (15). Similar approaches might benefit the management of ecologically complex and socially divisive issues such as tuberculosis in badgers, wolf predation on caribou, and hen harrier predation on grouse (4). The challenge, especially in more intense social conflicts over predators, is that polarized views may prevent parties from engaging with the process at all. If policy-makers, scientists, and stakeholders from all sides can show leadership in overcoming this challenge, predator management might become more evidence-based, as well as more responsive to changing social perspectives. ■ REFERENCES
1. G. Chapron et al., Science 346, 1517 (2014). 2. W. J. Ripple et al., Science 343, 151 (2014). 3. R. Woodroffe, S. Thirgood, A. R. Rabinowitz, People and Wildlife: Conflict or Coexistence? (Cambridge Univ. Press, Cambridge, 2005). 4. S. M. Redpath, R. J. Gutiérrez, K. A. Wood, J. C. Young, Conflicts in Conservation: Navigating Towards Solutions (Cambridge Univ. Press, Cambridge, 2015). 5. A. R. Holt, Z. G. Davies, C. Tyler, S. Staddon, PLOS ONE 3, 8 (2008). 6. R. K. Smith, A. S. Pullin, G. B. Stewart, W. J. Sutherland, Conserv. Biol. 24, 820 (2010). 7. S. N. Ellis-Felege, M. J. Conroy, W. E. Palmer, J. P. Carroll, J. Appl. Ecol. 49, 661 (2012). 8. K. M. Berger, E. M. Gese, J. Berger, Ecology 89, 818 (2008). 9. J. Bourne et al., Bovine TB: The Scientific Evidence (Defra, http://archive.defra.gov.uk/foodfarm/farmanimal/ diseases/atoz/tb/isg/report/final_report.pdf, London, 2007). 10. D. W. Macdonald, Rabies and Wildlife–a Biologist’s Perspective (Oxford Univ. Press, Oxford, 1980). 11. S. D. Cote, T. P. Rooney, J. P. Tremblay, C. Dussault, D. M. Waller, Annu. Rev. Ecol. Evol. Syst. 35, 113 (2004). 12. I. D. Trewby et al., Biol. Lett. 4, 170 (2008). 13. A. J. Novaro, R. S. Walker, in Large Carnivores and the Conservation of Biodiversity, J. C. Ray, K. H. Redford, R. S. Steneck, J. Berger, Eds. (Island Press, Washington, DC, 2005), pp. 268–288. 14. D. Hervieux, M. Hebblewhite, D. Stepnisky, M. Bacon, S. Boutin, Can. J. Zool. 92, 1029 (2014). 15. M. L. Gibeau, Wildl. Prof. 6, 62 (2012).
10.1126/science.aaa8465
1314
CELL BIOLOGY
An ESCRT to seal the envelope Cellular machinery that remodels different lipid bilayers also closes the nuclear membrane By Wesley I. Sundquist1 and Katharine S. Ullman2
M
etazoan cells divide by “open” mitosis, in which disassembly of the nucleus allows microtubules of the mitotic spindle to access kinetochores, proteinaceous structures that associate with specialized regions of chromosomes called centromeres. Duplicated chromosomes align on the spindle, and as they segregate toward opposite ends of the dividing cell, nuclear membrane reassembly initiates (1). This requires recruiting membrane, reconstituting nuclear pores, and severing microtubule connections between chromosomes and the spindle organizing centers (centrosomes). The nuclear envelope must seal to reestablish proper separation of the genome from the cytoplasm, but just how the nuclear membrane closes and overcomes the physical roadblocks presented by spindle microtubules has been unclear. Recent studies (2, 3) now demonstrate that the endosomal sorting complex required for transport (ESCRT) membrane fission machinery orchestrates this mysterious process. Membrane fission, the process by which a continuous lipid bilayer separates into two discontinuous bilayers, occurs constantly as cells remodel their membranes. It can occur with two distinct topologies: one in which the juxtaposing membranes are drawn together at a cytoplasm-filled neck, and another in which they are drawn together at a cytoplasm-surrounded neck. Many familiar processes, such as endocytic vesicle formation, correspond to the latter topology, where the cytoplasmic protein dynamin encircles the constricting neck and “pushes” the membranes toward the fission point. By contrast, ESCRT protein assemblies work from inside membrane necks to “pull” the constricting membranes toward themselves (4, 5). Two keys to this activity are the ability of ESCRT-III family members to form spiraling filaments that can draw membranes toward the fission point (6–8), and the ability of vacuolar protein sorting 4 (VPS4) to remodel these filaments and thereby provide the power for membrane fission (4, 5). ESCRT-III subunits also recruit relevant proteins through their exposed terminal
tails. Because of its unique activity, the ESCRT machinery is used in a variety of different membrane remodeling processes, including intraluminal vesicle formation in the late endosome, enveloped virus budding, wound healing, and the final stage of daughter cell physical separation (cytokinetic abscission) during cell division (4, 5, 9, 10). The studies by Vietri et al. (2) and Olmos et al. (3) reveal that the ESCRT pathway also reseals the nuclear envelope during late anaphase-early telophase stages of the cell division cycle (see the figure). The breakthrough was made possible, in part, because the investigators studied specific sites in the nuclear envelope at relevant times by combining live-cell imaging of transient events and higher-resolution
“Mechanisms that reseal the nuclear envelope have been unclear, but a role for ESCRT machinery should now be considered.” microscopic techniques, including structured illumination microscopy and correlative light and electron microscopy. The studies report that ESCRT-III and VPS4 assemble briefly at fenestrations in the growing nuclear envelope, and that assembly of core ESCRT-III subunits occurs in a canonical fashion, with component charged multivesicular body protein 4 (CHMP4), CHMP3, and CHMP2 proteins recruited sequentially (5). In the absence of successful ESCRT assembly, postmitotic nuclear envelopes have unsealed holes and are functionally “leaky.” Although the two studies agree on the essential role of ESCRT machinery in closing nuclear fenestrations, each also adds unique insights into this process. ESCRT-III proteins function at many different mem1
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA. 2Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5650, USA. E-mail: [email protected]; [email protected]
sciencemag.org SCIENCE
19 JUNE 2015 • VOL 348 ISSUE 6241
Published by AAAS
When the hunter becomes the hunted Rosie Woodroffe and Stephen M. Redpath Science 348, 1312 (2015); DOI: 10.1126/science.aaa8465
This copy is for your personal, non-commercial use only.
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here.
The following resources related to this article are available online at www.sciencemag.org (this information is current as of June 18, 2015 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/348/6241/1312.full.html This article cites 10 articles, 2 of which can be accessed free: http://www.sciencemag.org/content/348/6241/1312.full.html#ref-list-1 This article appears in the following subject collections: Ecology http://www.sciencemag.org/cgi/collection/ecology
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on June 18, 2015
Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here.
![[When the denture becomes dangerous!]](/assets/img/hold.png)
