Editorial
Special Issue: Membrane Trafficking
Membrane assembly and trafficking: destination Stockholm Danielle T. Loughlin (Editor) Trends in Cell Biology
I can still recall my first glimpse into cell biology. I was 10 years old and the teacher projected a schematic of an animal cell, explaining that cells are factories containing specialized compartments that perform distinct functions. During the lesson she discussed protein transport in the context of the secretory pathway originally discovered by George Palade and colleagues. She compared these cellular events to public transportation – each vesicle (bus) picks up cargo (people) and transports it to a designated destination either inside or outside the cell. Given the enormous advances made since then, today the basic model that my teacher described is rather a distant memory. However, it is important to bear in mind that the morphological roadmap of the secretory pathway that George Palade and colleagues created remained a relatively simple outline for many decades. Although it was accepted that secretory cargo is carried in small vesicles from the endoplasmic reticulum to the Golgi, and then to the cell surface, it was unclear how this process was achieved. If Palade was the original cartographer of membrane trafficking, then we can probably consider Randy Schekman, James Rothman, and Thomas Su¨dhof to be the engineers. Decades after Palade’s initial discoveries, Schekman, Rothman, and Su¨dhof demonstrated the molecular mechanisms underpinning these trafficking events, and in 2013 were awarded the Nobel Prize in Physiology or Medicine. In honor of their achievements, this special issue of Trends in Cell Biology is devoted to recent advances in the regulation of membrane biogenesis, cargo sorting, and vesicle trafficking. Using yeast genetics, Schekman identified the components governing vesicle formation and fusion in the early secretory pathway – including the Sec proteins that form the COP II coat – whereas Rothman, using biochemical techniques, classified proteins in mammalian cells that regulate vesicle docking and fusion in the Golgi. At the same time, Su¨dhof began delineating how neurotransmitters were released in a regulated manner by presynaptic neurons. Using biochemical and biophysical approaches he identified the machinery that responds to Ca2+ influx and allows precise fusion and release of neurotransmitters. Together, these three scientists established the molecular mechanisms underpinning cargo sorting, and vesicle formation and fusion. In this issue Juan Bonifacino provides Corresponding author: Loughlin, D.T. ([email protected]). 0962-8924/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tcb.2013.11.003
some perspective on the impact these studies have made on the field of membrane trafficking and on the unanswered questions that remain. Going a step further, we invited all three winners to talk about their perspective in a TrendsTalk, and we are delighted that Randy Schekman and Thomas Su¨dhof were able to contribute their views. The remaining reviews highlight advances in membrane assembly and trafficking that have arisen from this pioneering work, with an emphasis on areas where there is particular current interest. Focusing on the early secretory pathway, Antonella de Matteis and colleagues examine recent evidence of genetic diseases associated with defects in COPII machinery that prompt a re-evaluation of the mechanisms governing export carrier biogenesis. Closer to the cell surface, two groups review recent insights into different aspects of the mechanisms and roles of endocytic pathways. Jean Gruenberg and colleagues outline the role of the ESCRT-associated protein ALIX in intraluminal vesicle biogenesis and back-fusion with the limiting membrane, and suggest that these mechanisms may determine the final destination of vesicles. In the second article Clare Futter and colleagues discuss how endocytosis of the receptor tyrosine kinase EGFR, often dysregulated in cancer, coordinates mitogenic signaling and how current cancer therapies influence its trafficking. Regardless of the path that vesicles take, intracellular trafficking culminates in the fusion of transport vesicles with their target membranes. Covering this area, WanJin Hong and Sima Lev review how tethering factors promote the assembly of SNARE complexes during membrane fusion. Tethering factors are also involved in fusion events independent of vesicle formation, and Thomas Langer and colleagues provide evidence for how lipids are trafficked between the endoplasmic reticulum and mitochondria, or between mitochondrial membranes, via contact sites formed by tethering complexes. Membrane trafficking events extend beyond protein and lipid cargo to include the transport of organelles, which is essential for effective cell division and synapse formation. Two articles in this issue cover traffic at this organelle-based level. In one, Liza Pon and colleagues describe the mechanisms regulating mitochondrial inheritance in budding yeast, and in the other Francisco Sa´nchez-Madrid and colleagues examine how T lymphocyte activation dictates organelle location and ultimately asymmetric cell division. Trends in Cell Biology, January 2014, Vol. 24, No. 1
1
Editorial From an even broader perspective, vesicle trafficking is also involved in maintaining cellular homeostasis. Cells degrade damaged organelles and proteins in vesicles known as autophagosomes via fusion with lysosomes – a process known as autophagy. To highlight this area, James Hurley and colleagues examine recent structural evidence suggesting a role for the Atg multiprotein complex in regulating phagophore formation, the earliest step in autophagosome biogenesis.
2
Trends in Cell Biology January 2014, Vol. 24, No. 1
Collectively, these reviews are intended to highlight the enormous strides made in assembling an accurate roadmap of the pathway originally laid out by Palade, and emphasize the promising areas for future exploration. I would like to thank all the authors and reviewers for their contributions to this special issue and hope you enjoy reading it. I welcome your comments and ideas; you can always contact us with your feedback or questions at [email protected].
Special Issue: Membrane Trafficking
Membrane assembly and trafficking: destination Stockholm Danielle T. Loughlin (Editor) Trends in Cell Biology
I can still recall my first glimpse into cell biology. I was 10 years old and the teacher projected a schematic of an animal cell, explaining that cells are factories containing specialized compartments that perform distinct functions. During the lesson she discussed protein transport in the context of the secretory pathway originally discovered by George Palade and colleagues. She compared these cellular events to public transportation – each vesicle (bus) picks up cargo (people) and transports it to a designated destination either inside or outside the cell. Given the enormous advances made since then, today the basic model that my teacher described is rather a distant memory. However, it is important to bear in mind that the morphological roadmap of the secretory pathway that George Palade and colleagues created remained a relatively simple outline for many decades. Although it was accepted that secretory cargo is carried in small vesicles from the endoplasmic reticulum to the Golgi, and then to the cell surface, it was unclear how this process was achieved. If Palade was the original cartographer of membrane trafficking, then we can probably consider Randy Schekman, James Rothman, and Thomas Su¨dhof to be the engineers. Decades after Palade’s initial discoveries, Schekman, Rothman, and Su¨dhof demonstrated the molecular mechanisms underpinning these trafficking events, and in 2013 were awarded the Nobel Prize in Physiology or Medicine. In honor of their achievements, this special issue of Trends in Cell Biology is devoted to recent advances in the regulation of membrane biogenesis, cargo sorting, and vesicle trafficking. Using yeast genetics, Schekman identified the components governing vesicle formation and fusion in the early secretory pathway – including the Sec proteins that form the COP II coat – whereas Rothman, using biochemical techniques, classified proteins in mammalian cells that regulate vesicle docking and fusion in the Golgi. At the same time, Su¨dhof began delineating how neurotransmitters were released in a regulated manner by presynaptic neurons. Using biochemical and biophysical approaches he identified the machinery that responds to Ca2+ influx and allows precise fusion and release of neurotransmitters. Together, these three scientists established the molecular mechanisms underpinning cargo sorting, and vesicle formation and fusion. In this issue Juan Bonifacino provides Corresponding author: Loughlin, D.T. ([email protected]). 0962-8924/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tcb.2013.11.003
some perspective on the impact these studies have made on the field of membrane trafficking and on the unanswered questions that remain. Going a step further, we invited all three winners to talk about their perspective in a TrendsTalk, and we are delighted that Randy Schekman and Thomas Su¨dhof were able to contribute their views. The remaining reviews highlight advances in membrane assembly and trafficking that have arisen from this pioneering work, with an emphasis on areas where there is particular current interest. Focusing on the early secretory pathway, Antonella de Matteis and colleagues examine recent evidence of genetic diseases associated with defects in COPII machinery that prompt a re-evaluation of the mechanisms governing export carrier biogenesis. Closer to the cell surface, two groups review recent insights into different aspects of the mechanisms and roles of endocytic pathways. Jean Gruenberg and colleagues outline the role of the ESCRT-associated protein ALIX in intraluminal vesicle biogenesis and back-fusion with the limiting membrane, and suggest that these mechanisms may determine the final destination of vesicles. In the second article Clare Futter and colleagues discuss how endocytosis of the receptor tyrosine kinase EGFR, often dysregulated in cancer, coordinates mitogenic signaling and how current cancer therapies influence its trafficking. Regardless of the path that vesicles take, intracellular trafficking culminates in the fusion of transport vesicles with their target membranes. Covering this area, WanJin Hong and Sima Lev review how tethering factors promote the assembly of SNARE complexes during membrane fusion. Tethering factors are also involved in fusion events independent of vesicle formation, and Thomas Langer and colleagues provide evidence for how lipids are trafficked between the endoplasmic reticulum and mitochondria, or between mitochondrial membranes, via contact sites formed by tethering complexes. Membrane trafficking events extend beyond protein and lipid cargo to include the transport of organelles, which is essential for effective cell division and synapse formation. Two articles in this issue cover traffic at this organelle-based level. In one, Liza Pon and colleagues describe the mechanisms regulating mitochondrial inheritance in budding yeast, and in the other Francisco Sa´nchez-Madrid and colleagues examine how T lymphocyte activation dictates organelle location and ultimately asymmetric cell division. Trends in Cell Biology, January 2014, Vol. 24, No. 1
1
Editorial From an even broader perspective, vesicle trafficking is also involved in maintaining cellular homeostasis. Cells degrade damaged organelles and proteins in vesicles known as autophagosomes via fusion with lysosomes – a process known as autophagy. To highlight this area, James Hurley and colleagues examine recent structural evidence suggesting a role for the Atg multiprotein complex in regulating phagophore formation, the earliest step in autophagosome biogenesis.
2
Trends in Cell Biology January 2014, Vol. 24, No. 1
Collectively, these reviews are intended to highlight the enormous strides made in assembling an accurate roadmap of the pathway originally laid out by Palade, and emphasize the promising areas for future exploration. I would like to thank all the authors and reviewers for their contributions to this special issue and hope you enjoy reading it. I welcome your comments and ideas; you can always contact us with your feedback or questions at [email protected].
