Held at Glasgow Caledonian University, Glasgow, U.K., 5 December 2014.
Overview of the 8th UK Gap Junction meeting – 5th December 2014 Scott J. Johnstone*, Catherine S. Wright† and Patricia E. Martin†1 *College of Medical, Veterinary and Life Sciences, University of Glasgow, British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow, G12 8TA, U.K. †Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, U.K.
Abstract The 8th UK Gap Junction meeting was held in Glasgow Caledonian University (GCU) on 5th December 2014. Emeritus Professor Howard Evans presented an overview of 50 years of gap junction research whereas Dr Brant Isakson, University of Virginia, discussed the intriguing role of recently identified pannexin proteins in endothelial function. Forty-five delegates from across the U.K. and the Europe attended the day with 12 talks from young researchers and five posters. This issue of biochemical transactions provides an overview of the highlights of the work discussed throughout the day.
Organizer overview The UK Gap Junction meetings have been regular events for the last 18 years, bringing together researchers within the field across the U.K. (Table 1). These informal gatherings have provided scope for exchange of ideas and graduate experience in the years in between the bi-annual International Gap Junction Conferences, which are usually held at alternating sites between the U.S.A. and Europe. The 2015 meeting will be held in March 2015 in Chile (http://cinv.uv.cl/igjc2015/) with the 2017 meeting to be hosted in Glasgow (http://igjc2017.com). Connexins are tetramembrane spanning proteins that form hemichannels in the plasma membrane and ultimately align to form gap junction cell–cell communication channels between neighbouring cells. In the last 10 years, a family of structurally related proteins that also form hemichannels, the pannexins, has been identified. It emerges that both channels are dynamically regulated in diverse tissue systems, are remodelled during disease and are increasingly being recognized as therapeutic targets. The 2014 UK Gap Junction meeting, held at Glasgow Caledonian University (GCU) and supported by the Biochemical Society, Zealand Pharma, GCU and Glasgow University, attracted 45 delegates from across the U.K., Key words: connexin, pannexin, gap junction. Abbreviations: Cx26, connexin 26; Cx32, connexin 32; Cx43, connexin 43; ECR, early career researcher; GCU, Glasgow Caledonian University; IGJC, international gap junction conference; KID, keratitis ichthyosis syndrome; Panx 1, pannexin 1. 1 To whom correspondence should be addressed (email: [email protected]).
Biochem. Soc. Trans. (2015) 43, 447–449; doi:10.1042/BST20150038
8th UK Gap Junction Meeting
8th UK Gap Junction Meeting
along with the European visitors from Denmark, Spain and Portugal. There were 12 talks, delivered mostly by young graduate and ECR researchers. We were delighted that Emeritus Professor Howard Evans (University of Cardiff) and Dr Brant Isakson (University of Virginia) delivered keynote talks. There were three sessions focusing on connexin history structure and function, vascular connexins and pannexins and connexins and channel gating. Professor Howard Evans, a pioneer in the understanding of gap junction structure and function gave the first keynote speech on the 50 year history of the gap junction field. Howard gave a vibrant talk describing the very first discovery of the gap junctions and of many of the initial studies regarding identification of connexins, the constituent proteins of these intercellular channels. He stressed many of the struggles that early researchers in the field went through in order to identify the function of these ‘low resistance channels’ in regulating cell-to-cell communication. Professor Evans highlighted the importance of gap junctions and connexin hemichannels in the regulation of cardiac and vascular function and described the role for these in cellular physiology. Professor Evans’ group was the first to generate connexin mimetic peptides that have emerged as blockers of hemichannel and gap junction channel function, widely used today. He also emphasized the importance of the identification of connexin 32 (Cx32) and connexin 26 (Cx26) mutations in human disease; and the development of connexin-chimeric proteins linked to aequorin and GFP as reporters that have helped to illuminate the dynamics of these proteins in real time (review 1). C The
Authors Journal compilation
C 2015
Biochemical Society
447
448
Biochemical Society Transactions (2015) Volume 43, part 3
Table 1 History of the UK Gap Junction meetings IGJC, international gap junction conference. Year
Location
Organizer
Invited keynote speaker
1998
Queen Mary College, London
Professor David Kelsell
–
2000 2002 2004
University College London University College London University of Cardiff
Professor David Becker Professor Nick Severs Professor Howard Evans
– – Professor Luc Leybaert, University of Ghent,
2006
GCU
Dr Patricia Martin
organizer of IGJC 2011 Professor Dale Laird, University of Ontario, Canada, organizer of IGJC 2009
2008 2012 2014
University of Surrey GCU GCU
Dr Ernesto Oviedo-Orta and Dr Patricia Martin Dr Patricia Martin Dr Scott Johnstone, Dr Catherine Wright and Dr
Professor Brenda Kwak, University of Geneva Professor Paulo Meda, University of Geneva Professor Howard Evans and Dr Brant Isakson
Patricia Martin
Each of the subsequent talks by graduate students was judged by Emeritus Professors Howard Evans (University of Cardiff) and Malcolm Hodgins (University of Glasgow/GCU) and Professor Sheila Graham (University of Glasgow), all key members of the UK Gap Junction community. First prize was awarded to Louise Meigh, a final year PhD student from the University of Warwick on her novel findings illustrating that Cx26 plays a pivotal role in sensing pCO2 levels in the brain. Using a structure function approach and naturally occurring mutations in Cx26 associated with keratitis ichthyosis deafness (KID) syndrome, the Warwick team have identified that carbonylation of lysine residues (Lys125 ) lining the pore of the Cx26 channel provide a pocket for CO2 binding. Further analysis suggests that mutations arising in KID syndrome have lost the ability to bind CO2 and may contribute to disease pathology (review 2). Claudia Salat, a PhD student, from the Vall d’Hebron Institut de Recerca in Barcelona gave an eloquent talk describing recent data on identification of an internal transcription start site enabling expression of a connexin 43 (Cx43)-C-terminal protein of 20 kDa. For many years, this 20 kDa band has been observed by researchers and was thought to have been an antibody artifact or a cleavage product. Along with other recently published work, Claudia has revealed that this ‘short Cx43 segment’ is specifically expressed in cells through cap-mediated internal translation (review 3). A group led by Dr Henrique Girao from the University of Combria, Portugal, attending their first Gap Junction meeting presented two talks by PhD students, where they discussed their data on ubiquitination and the role of autophagy in Cx43 degradation and turnover in the heart during ischaemia (reviews 4 and 5). Claire Lorraine, a final year PhD student from GCU detailed her studies on the role of connexins in wound healing events. Many studies over the years have shown that reduction in Cx43 at the wound edge can lead to an enhanced wound healing and reduced scar formation in humans. Using Gap27 peptides, C The
C 2015 Biochemical Society Authors Journal compilation
identified by Professor Evans, the GCU group has shown that these peptides provide a powerful tool to dissect the role of Cx43 in cell migration and adhesion events (review 6). Professor Jonathon Gibbins, from the University of Reading, discussed his group’s data on the way in which connexins and gap junctions are involved in regulating thrombus formation and retraction, events particularly important in atherosclerosis, again illustrating the importance of connexin mimetic peptides as tools for probing roles of connexins in regulating tissue events (review 7). Dr Brant Isakson, University of Virginia, gave the second keynote talk introducing a role for pannexins in regulating vascular function and how these hemichannels can regulate the acute inflammatory response in the endothelium. Dr Isakson has a long history in the gap junction field, having carried out his PhD in the laboratory of Professor Scott Boitano looking at gap junction signalling in lung epithelial cells. During these studies, he spent time in Professor Evans’ laboratory in Cardiff and this was followed by a move to the laboratory of Professor Brian Duling where he studied the role of the gap junctions in the myoendothelial junction, linking smooth muscle cells to endothelial cells. Over the years, Brant’s work has shifted in focus from connexin to pannexin channels as regulators of vascular function through release of ATP to the extracellular space. Brant’s talk focused on the acute inflammatory response in the microvasculature, capillaries and arterioles, an area that is gaining increased attention (review 8). Several other talks focused on connexins and pannexins in vascular function. Kirk Taylor, who has recently completed his PhD studies at Leicester University, gave an illuminating talk demonstrating that pannexin 1 (Panx 1) is expressed on the surface of platelets. Histidine studies suggest that Panx 1 contributes to thrombus formation and that inhibiting the channel can limit thrombus size (review 9) and complemented studies by the Gibbins group (review 7). Biochem. Soc. Trans. (2015) 43, 448–449; doi:10.1042/BST20150038
8th UK Gap Junction Meeting
Line Waring, a PhD student from the University of Copenhagen, described how the carboxy tail of Cx43 is required for correct trafficking and function of the sodium channel NAV1.5, possibly via a phosphorylation-specific event on Cx43 (review 10). Finally several talks by early career students looked at the role of connexins and pannexins in cardiovascular disease and the innate immune response. Lisa McAuthur, from University of Glasgow, won the best ‘new start’ talk outlining her initial studies and plans for her PhD on the role that Cx43 expression in fibroblasts plays in scarring and cardiac arrhythmias (review 11). Dr Nanna MacAuley gave a lively talk addressing connexin phosphorylation, hemichannel signalling in astrocytes and
their potential role as water-permeable channels (review 12). Five other students presented posters of their work, enabling discussion through coffee breaks and the reception. All talks were followed by active discussions, and the day ended with a wine and cheese reception and dinner at an Italian restaurant in the heart of Glasgow, which provided and excellent opportunity for networking and for new collaborations to be made. This issue of Biochemical Society Transactions highlights review articles of the work that was discussed during the day. Received 5 February 2015 doi:10.1042/BST20150038
C The
C 2015 Biochemical Society Authors Journal compilation
449
Overview of the 8th UK Gap Junction meeting – 5th December 2014 Scott J. Johnstone*, Catherine S. Wright† and Patricia E. Martin†1 *College of Medical, Veterinary and Life Sciences, University of Glasgow, British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow, G12 8TA, U.K. †Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, U.K.
Abstract The 8th UK Gap Junction meeting was held in Glasgow Caledonian University (GCU) on 5th December 2014. Emeritus Professor Howard Evans presented an overview of 50 years of gap junction research whereas Dr Brant Isakson, University of Virginia, discussed the intriguing role of recently identified pannexin proteins in endothelial function. Forty-five delegates from across the U.K. and the Europe attended the day with 12 talks from young researchers and five posters. This issue of biochemical transactions provides an overview of the highlights of the work discussed throughout the day.
Organizer overview The UK Gap Junction meetings have been regular events for the last 18 years, bringing together researchers within the field across the U.K. (Table 1). These informal gatherings have provided scope for exchange of ideas and graduate experience in the years in between the bi-annual International Gap Junction Conferences, which are usually held at alternating sites between the U.S.A. and Europe. The 2015 meeting will be held in March 2015 in Chile (http://cinv.uv.cl/igjc2015/) with the 2017 meeting to be hosted in Glasgow (http://igjc2017.com). Connexins are tetramembrane spanning proteins that form hemichannels in the plasma membrane and ultimately align to form gap junction cell–cell communication channels between neighbouring cells. In the last 10 years, a family of structurally related proteins that also form hemichannels, the pannexins, has been identified. It emerges that both channels are dynamically regulated in diverse tissue systems, are remodelled during disease and are increasingly being recognized as therapeutic targets. The 2014 UK Gap Junction meeting, held at Glasgow Caledonian University (GCU) and supported by the Biochemical Society, Zealand Pharma, GCU and Glasgow University, attracted 45 delegates from across the U.K., Key words: connexin, pannexin, gap junction. Abbreviations: Cx26, connexin 26; Cx32, connexin 32; Cx43, connexin 43; ECR, early career researcher; GCU, Glasgow Caledonian University; IGJC, international gap junction conference; KID, keratitis ichthyosis syndrome; Panx 1, pannexin 1. 1 To whom correspondence should be addressed (email: [email protected]).
Biochem. Soc. Trans. (2015) 43, 447–449; doi:10.1042/BST20150038
8th UK Gap Junction Meeting
8th UK Gap Junction Meeting
along with the European visitors from Denmark, Spain and Portugal. There were 12 talks, delivered mostly by young graduate and ECR researchers. We were delighted that Emeritus Professor Howard Evans (University of Cardiff) and Dr Brant Isakson (University of Virginia) delivered keynote talks. There were three sessions focusing on connexin history structure and function, vascular connexins and pannexins and connexins and channel gating. Professor Howard Evans, a pioneer in the understanding of gap junction structure and function gave the first keynote speech on the 50 year history of the gap junction field. Howard gave a vibrant talk describing the very first discovery of the gap junctions and of many of the initial studies regarding identification of connexins, the constituent proteins of these intercellular channels. He stressed many of the struggles that early researchers in the field went through in order to identify the function of these ‘low resistance channels’ in regulating cell-to-cell communication. Professor Evans highlighted the importance of gap junctions and connexin hemichannels in the regulation of cardiac and vascular function and described the role for these in cellular physiology. Professor Evans’ group was the first to generate connexin mimetic peptides that have emerged as blockers of hemichannel and gap junction channel function, widely used today. He also emphasized the importance of the identification of connexin 32 (Cx32) and connexin 26 (Cx26) mutations in human disease; and the development of connexin-chimeric proteins linked to aequorin and GFP as reporters that have helped to illuminate the dynamics of these proteins in real time (review 1). C The
Authors Journal compilation
C 2015
Biochemical Society
447
448
Biochemical Society Transactions (2015) Volume 43, part 3
Table 1 History of the UK Gap Junction meetings IGJC, international gap junction conference. Year
Location
Organizer
Invited keynote speaker
1998
Queen Mary College, London
Professor David Kelsell
–
2000 2002 2004
University College London University College London University of Cardiff
Professor David Becker Professor Nick Severs Professor Howard Evans
– – Professor Luc Leybaert, University of Ghent,
2006
GCU
Dr Patricia Martin
organizer of IGJC 2011 Professor Dale Laird, University of Ontario, Canada, organizer of IGJC 2009
2008 2012 2014
University of Surrey GCU GCU
Dr Ernesto Oviedo-Orta and Dr Patricia Martin Dr Patricia Martin Dr Scott Johnstone, Dr Catherine Wright and Dr
Professor Brenda Kwak, University of Geneva Professor Paulo Meda, University of Geneva Professor Howard Evans and Dr Brant Isakson
Patricia Martin
Each of the subsequent talks by graduate students was judged by Emeritus Professors Howard Evans (University of Cardiff) and Malcolm Hodgins (University of Glasgow/GCU) and Professor Sheila Graham (University of Glasgow), all key members of the UK Gap Junction community. First prize was awarded to Louise Meigh, a final year PhD student from the University of Warwick on her novel findings illustrating that Cx26 plays a pivotal role in sensing pCO2 levels in the brain. Using a structure function approach and naturally occurring mutations in Cx26 associated with keratitis ichthyosis deafness (KID) syndrome, the Warwick team have identified that carbonylation of lysine residues (Lys125 ) lining the pore of the Cx26 channel provide a pocket for CO2 binding. Further analysis suggests that mutations arising in KID syndrome have lost the ability to bind CO2 and may contribute to disease pathology (review 2). Claudia Salat, a PhD student, from the Vall d’Hebron Institut de Recerca in Barcelona gave an eloquent talk describing recent data on identification of an internal transcription start site enabling expression of a connexin 43 (Cx43)-C-terminal protein of 20 kDa. For many years, this 20 kDa band has been observed by researchers and was thought to have been an antibody artifact or a cleavage product. Along with other recently published work, Claudia has revealed that this ‘short Cx43 segment’ is specifically expressed in cells through cap-mediated internal translation (review 3). A group led by Dr Henrique Girao from the University of Combria, Portugal, attending their first Gap Junction meeting presented two talks by PhD students, where they discussed their data on ubiquitination and the role of autophagy in Cx43 degradation and turnover in the heart during ischaemia (reviews 4 and 5). Claire Lorraine, a final year PhD student from GCU detailed her studies on the role of connexins in wound healing events. Many studies over the years have shown that reduction in Cx43 at the wound edge can lead to an enhanced wound healing and reduced scar formation in humans. Using Gap27 peptides, C The
C 2015 Biochemical Society Authors Journal compilation
identified by Professor Evans, the GCU group has shown that these peptides provide a powerful tool to dissect the role of Cx43 in cell migration and adhesion events (review 6). Professor Jonathon Gibbins, from the University of Reading, discussed his group’s data on the way in which connexins and gap junctions are involved in regulating thrombus formation and retraction, events particularly important in atherosclerosis, again illustrating the importance of connexin mimetic peptides as tools for probing roles of connexins in regulating tissue events (review 7). Dr Brant Isakson, University of Virginia, gave the second keynote talk introducing a role for pannexins in regulating vascular function and how these hemichannels can regulate the acute inflammatory response in the endothelium. Dr Isakson has a long history in the gap junction field, having carried out his PhD in the laboratory of Professor Scott Boitano looking at gap junction signalling in lung epithelial cells. During these studies, he spent time in Professor Evans’ laboratory in Cardiff and this was followed by a move to the laboratory of Professor Brian Duling where he studied the role of the gap junctions in the myoendothelial junction, linking smooth muscle cells to endothelial cells. Over the years, Brant’s work has shifted in focus from connexin to pannexin channels as regulators of vascular function through release of ATP to the extracellular space. Brant’s talk focused on the acute inflammatory response in the microvasculature, capillaries and arterioles, an area that is gaining increased attention (review 8). Several other talks focused on connexins and pannexins in vascular function. Kirk Taylor, who has recently completed his PhD studies at Leicester University, gave an illuminating talk demonstrating that pannexin 1 (Panx 1) is expressed on the surface of platelets. Histidine studies suggest that Panx 1 contributes to thrombus formation and that inhibiting the channel can limit thrombus size (review 9) and complemented studies by the Gibbins group (review 7). Biochem. Soc. Trans. (2015) 43, 448–449; doi:10.1042/BST20150038
8th UK Gap Junction Meeting
Line Waring, a PhD student from the University of Copenhagen, described how the carboxy tail of Cx43 is required for correct trafficking and function of the sodium channel NAV1.5, possibly via a phosphorylation-specific event on Cx43 (review 10). Finally several talks by early career students looked at the role of connexins and pannexins in cardiovascular disease and the innate immune response. Lisa McAuthur, from University of Glasgow, won the best ‘new start’ talk outlining her initial studies and plans for her PhD on the role that Cx43 expression in fibroblasts plays in scarring and cardiac arrhythmias (review 11). Dr Nanna MacAuley gave a lively talk addressing connexin phosphorylation, hemichannel signalling in astrocytes and
their potential role as water-permeable channels (review 12). Five other students presented posters of their work, enabling discussion through coffee breaks and the reception. All talks were followed by active discussions, and the day ended with a wine and cheese reception and dinner at an Italian restaurant in the heart of Glasgow, which provided and excellent opportunity for networking and for new collaborations to be made. This issue of Biochemical Society Transactions highlights review articles of the work that was discussed during the day. Received 5 February 2015 doi:10.1042/BST20150038
C The
C 2015 Biochemical Society Authors Journal compilation
449
