- Email: [email protected]
Signal transduction during biomembrane fusion
MISCELLANEA
prostagland.ns and thromboxanes) cover the generation of the messengers. By this stage the book has already reflected the complexity of the networks studied although partofthe chapter on PIC continues the orderly 'inward' progression from G proteins, the larger part deals with the alternative route of stimulation, starting at receptor tyrosine kinases, which activate PIC¥1 rather than PIC~I. Subsequently, the principal intracellular receptor/mediator proteins are dealt with - the cyclic-nucleotidedependent protein kinases, protein kinase C, inositol phosphate receptors and (after another short diversion back to the membrane for Caz* entry) calmoduhn. In chapters 12 to 14 the quiescent state is restored by the cyclic-nucleotlde phosphodiesterases, the metabolism of diacylglycerol and inositol phosphates, and the removal of Caz* from the cytosol. However, Caz* signals immediately bounce back in chapter 1,Swith a discussion of their spatial and temporal organization, and Caz* also features strongly in Tim Cheek's discussion of the regulation of secretion in chromaifin cells. Finally, Simon Morley and George Thomas describe the molecular machinery of protein synthesis, and its possible regulation during the mltogenic
Focus on m e m b r a n e fusion Signal Transduction during Biomembrane Fusion edlfed by Danton H. O'Day, Academic Press, 1993. £64.00 (265 pages) ISBN0 12 524155 0 Sometimes people ask me what we work on and I find myself at a loss for the succinct statement. Maybe the short answer to this question is 'signal transduction during biomembrane fusion', the title of this recent book edited by Danton O'Day of the University of Toronto. In addition to an introductory 'overview', O'Day himself contributes two further chaptees: one on phagocytic mechanisms, the other on cell fusion. In this way he and his colleagues figure in all three main sections of the book, which are devoted to fusion mechanisms, intra-
response and meiotic maturation This chapter is rather different from the others, and gives a flavour of the downstream signalling cascades or networks involving (principally) phosphorylation. Given the closely related nature of the material, there is inevitably some repetition between chapters (we are treated to several versions of the basic G-protein cycle), but this is quite hmIted. As for omissions, th~=seare significant only in the fastest-moving fields. For example, the concept that Src homology SH2 domains are involved in the recruitment of PIC71 and other proteins by receptor tyrosine kinases is included, but the details of the interactLons are not. Additionally, the remit of the book entails the omission, or only brief mention, of several prominent signalling topics (e.g. Ras, cyclins, 3-phosphorylated inositol lipids). The 1 7 chapters are mostly between 15 and 25 pages in length (plus extensive reference lists), which makes them long enough to be reasonably comprehensive ,vlthout being daunting. Each can be read separately, without reference to the others; indeed, there is little or no cross-referencing between chapters, other than ~ia the index (which is perhaps a little sparse). The writing is generally very good,
and quite uniform .n style for such a multi-author volume The only irritation, in some chapters more than others, is a fairly high error rate. Some of these are trivial, and are readily interpreted by the context, but others [e.g. Ins(1,4,S)P4Jare scientifically significant and really should have been detected. Who will (or should) read th,s book? (It has certainly raised a fair amount of interest among the local signalling fraternity passing my desk ) The answer is: anyone who is looking for a solid review of the topics covered, rather than the latest linkage of receptor X to an adaptor Y cloned by homology to a hitherto obscure protein from Caenorhubdltls elegans. As hinted at above, books of this type share a common problem their preparation time prevents competition with the many minirev,ews now available in monthly journals, such as the Trends and Current Opinion series. They must compete instead at the level of Annual Rewews, and score by collecting related articles into one coherent volume, to act as a reference 'bible' for the lab or the teaching shelf. To that extent, Intracellular Messengers does very well, and I came away from chapters on less-famihar topics with a feel. ing of being well informed.
cellular membrane fusion and cell fusion. There are 12 cllapters. A strong editorial hand Is clear. Not only are all the contributions brief and to the poht (none Is longer than 22 pages) but they all share a common format, being divided Into sections entitled Introduction, Current Research and Final Comments. Hawng been involved in the study of exocytotic mechanisms for several years, I thought that by now ! would know most of the personalities in the field. Not sol It was a bit of a surprise to find that few of the authors 0ncludmg the editor) were known to me, even by reputation. This then, is not the team that I could have .~plected were I sitting in the editor's chair How well do they stand up? My impression is that the further removed the chaprers are from my own interests, the more informative and more authoritative they become. Thus, the prehminary overview by O'Day yields little useful inforn~ation abuu" [uslon processes, and he receives scant support from the other authors in this initial section. It seems to me that Knoll and Plattn~r were more concerned to re-
establish priority for their idea of the focal interacUon between fusin§ membranes than to address the frontiers of their subject. For most people, the main argument here was settled around 1980 by the work of Chandler and Heuser and, as far as I know, they were the first to use the term fusion pore. Maybe the Plattner group did get in first, and maybe there are old scores to settle, but it doesn't make for a very engrossing essay, especially coming from a group that continues to rr~'~, important contribution,. Lt,c)'s chapter is marred by careless proof reading (even to the point of misspelling his own name in the reference list). He seems to be out of touch with the most important recent developments in the field and I am not certain that he has really accepted the idea that interacting membranes undergoing fusion make contact only at very discrete 'focal' points. Altogether, th~s section is weak It needed a chapter from a theoretician - one who could explain the stability of the lipid bilayer and the energetic considerations that make contact at molecular feel.~g distance so
TRENDS IN CELL BIOLOGYVOL. 4 JANUARY 1.994
Anthony N. Corps Departmentof Cellular Physiology,AFRC Babraham InsUtute, Sabraham, Cambridge,UK CB2 4AT.
31
MISCELLANEA
gl. Do Gomperts Departmentof Physiology, UnlvemtyCollege London, Rockefeller Building, UniversityStreet, London,UK WCIE 6h
32
improbable. Even more importantly, it [,.=ededa contribution from one of the electrophysmlogists, to describe the earliest steps in the formation of the fusion pore, at the stage when its dimensions are too small to resolve by morphological methods. Indeed, the technique of whole-cell patchclamping gets hardly a mention =n this book and yet it is the practitioners in this field who have contributed more than anyone else to the understanding of membrane fusion in the last few years Intracellular processes of membrane fusion are presented with respect to some of the weU-known systems. There is an informative chapter describing exocytosls in eggs (Khne) and rather hght-weight contributions on mast cells (Koopman) and platelets (Gerard et al.). Many of the permutations and combinations of Caz*, GTP, phorbol esters, staurosporin, protein kinase C, and phosphohpases of many colours are on show here, but I didn't find much to challenge the mind. The best chapter in this section is by Anja Leyte and her colleagues from the Cell Biology Program at EMBL. In a dozen pages or so, they give an excellent resum6 of the goings on in the trons Golgl network and nearby compartments. The idea that heterotrimerlc and mono. merit GTP-blnding proteins interact to control, and then to ensure accuracy of, membrane fusion Is one that is going to be around for some time to come. Phagocytosls (Lewis, Browning and O'Day) is discussed mainly from the viewpoint of the protozoans. I get the feeling that O'Day stands here on much firmer ground than in his introductory overview. The third section, on cell fusion, commences with three chapters on myotube formation. There is Priveson the control and role of Caz*, followed by Sauro and Strickland who concentrate on phosphohpid metabolism (and CaZ*), and then David and Fitzpatrick on protein phosphorylation (with still more Ca2*). If I wanted to learn about skeletal muscle development, this book would be a useful starting point The final chapter finds O'Day (this time with Lydan) obviously on home territory with Dictyostelium. Yet again, Ca2÷ figures as an Important mediator of membrane fusion as it has for at least the last 50 (I am tempted to say 100) ye,*r;. A notable absence from the book is an account of the fusion of sperm with egg. A good description of this process could have disposed of
the idea that fusion between cells is driven by osmotic forces. It could also have killed the notion that Ca2* is an essential ingredient for the all cell-cell fusions in short, while Ca2* was needed for the readers of this journal to make their start in life, sea urchins get by without. After all this time it is remarkable how few clues we have concerning the identity of the CaZ*-bindlng proterns that mediate membrane fusion. Even more remarkable is how few authors are prepared to face up to the challenge and think about what it is that Caz* and its unidentified binding proteins might actually do. Quite clearly, although its site of action is always intracellular, its function must be quite different for intracellular
Encompassing ceils and organelles Molecular Biology of Membranes', Structure and Function by Howard R. Petty, Plenum Publishing, 1993. $.~9.50 (379 pages) ISBN 0 306 44429 1 The last few years have seen a rapid proliferation of our knowledge of the molecular basis of biological membrane function. While some of the new informal.ion has found its way into the latest edlbons of general bio. chemi~i.ly L~xts, there is clearly a need for a new comprehensive book to accompany courses on membranes for undergraduates and begmning postgraduates. Students and teachers of such courses will therefore welcome Howard Petty's book, which is prl. marily aimed at just such an audience. The book essentially consists of two halves, After a brief introduction, three chapters describe the structure and molecular assembly of lipids, carbohydrates and proteins that form the principal components of biological membranes, One chapter is devoted to electron microscopy and crystallographic methods of studying struc. ture, but spectroscopic techniques are not included. The remaining five chapters are concerned with function. The topics covered include energy transduction, transport, receptors,
fusions and extrac,llular fusions In the latter situabon the Ca2. that matters is absent from contact zones between the fusing surfaces. Thus, although Ca2. appears as a common theme almost throughout this book, linking the various systems, we should not be deluded into believing that it always plays the same game. I would have preferred to concentrate on events either on the inside or on the outside, and then to seek some of the exceptions to the rules such as Ca2*inhibited fusion, Na*-mduced fusion and cAMP-induced fusion in the three Ps (i.e Parathyroid, Pituitary and Parotid) By distancing ourselves from Caz* we might actually get a better idea of why it appears to be so good for membrane fusion.
fusion and membrane biosynthesis, while a final chapter discusses the involvement of membranes in cancer. A major impetus to membrane research over the past few years has been the increasing application of molecular genetic techniques. Although there is no specific chapter on this approach, there are numerous references to ~tthroughout the book For example, the transport chapter contains a description of Kaback's sitedirected mutagenesls experiments with lac permease, and genetic analysis of protein targeting is discussed under membrane formation, I have some reservations about the part of the book on molecular strut. tures. Undoubtedly much of the current excitement in membrane reseal~1~arises from progress towards elucidating the three-dimensional structure of membrane proteins. Unfortunately, the treatment of this key topic is not well organized, with essential material spread over several chapters. Surely the structure of the bacterial photosynthetic reaction centre, whose determination was a lan,imark in membrane research, should have appeared in the first part of the book rather than in a later chapter on bioenergetics. Furthermore, the 1975 Henderson and Unwin model of bacteriorhodopsin is presented rather than the higher-resolution 1990 model that.gives much insight into the molecular mechanism of proton pumping, The transmembrane ~-helix as a probable key structural component would benefit from more emphasis and curiously is not mentioned until after a discussion of membrane protein topology.
TRENDS IN CELLBIOLOGYVOL 4 JANUARY1994
prostagland.ns and thromboxanes) cover the generation of the messengers. By this stage the book has already reflected the complexity of the networks studied although partofthe chapter on PIC continues the orderly 'inward' progression from G proteins, the larger part deals with the alternative route of stimulation, starting at receptor tyrosine kinases, which activate PIC¥1 rather than PIC~I. Subsequently, the principal intracellular receptor/mediator proteins are dealt with - the cyclic-nucleotidedependent protein kinases, protein kinase C, inositol phosphate receptors and (after another short diversion back to the membrane for Caz* entry) calmoduhn. In chapters 12 to 14 the quiescent state is restored by the cyclic-nucleotlde phosphodiesterases, the metabolism of diacylglycerol and inositol phosphates, and the removal of Caz* from the cytosol. However, Caz* signals immediately bounce back in chapter 1,Swith a discussion of their spatial and temporal organization, and Caz* also features strongly in Tim Cheek's discussion of the regulation of secretion in chromaifin cells. Finally, Simon Morley and George Thomas describe the molecular machinery of protein synthesis, and its possible regulation during the mltogenic
Focus on m e m b r a n e fusion Signal Transduction during Biomembrane Fusion edlfed by Danton H. O'Day, Academic Press, 1993. £64.00 (265 pages) ISBN0 12 524155 0 Sometimes people ask me what we work on and I find myself at a loss for the succinct statement. Maybe the short answer to this question is 'signal transduction during biomembrane fusion', the title of this recent book edited by Danton O'Day of the University of Toronto. In addition to an introductory 'overview', O'Day himself contributes two further chaptees: one on phagocytic mechanisms, the other on cell fusion. In this way he and his colleagues figure in all three main sections of the book, which are devoted to fusion mechanisms, intra-
response and meiotic maturation This chapter is rather different from the others, and gives a flavour of the downstream signalling cascades or networks involving (principally) phosphorylation. Given the closely related nature of the material, there is inevitably some repetition between chapters (we are treated to several versions of the basic G-protein cycle), but this is quite hmIted. As for omissions, th~=seare significant only in the fastest-moving fields. For example, the concept that Src homology SH2 domains are involved in the recruitment of PIC71 and other proteins by receptor tyrosine kinases is included, but the details of the interactLons are not. Additionally, the remit of the book entails the omission, or only brief mention, of several prominent signalling topics (e.g. Ras, cyclins, 3-phosphorylated inositol lipids). The 1 7 chapters are mostly between 15 and 25 pages in length (plus extensive reference lists), which makes them long enough to be reasonably comprehensive ,vlthout being daunting. Each can be read separately, without reference to the others; indeed, there is little or no cross-referencing between chapters, other than ~ia the index (which is perhaps a little sparse). The writing is generally very good,
and quite uniform .n style for such a multi-author volume The only irritation, in some chapters more than others, is a fairly high error rate. Some of these are trivial, and are readily interpreted by the context, but others [e.g. Ins(1,4,S)P4Jare scientifically significant and really should have been detected. Who will (or should) read th,s book? (It has certainly raised a fair amount of interest among the local signalling fraternity passing my desk ) The answer is: anyone who is looking for a solid review of the topics covered, rather than the latest linkage of receptor X to an adaptor Y cloned by homology to a hitherto obscure protein from Caenorhubdltls elegans. As hinted at above, books of this type share a common problem their preparation time prevents competition with the many minirev,ews now available in monthly journals, such as the Trends and Current Opinion series. They must compete instead at the level of Annual Rewews, and score by collecting related articles into one coherent volume, to act as a reference 'bible' for the lab or the teaching shelf. To that extent, Intracellular Messengers does very well, and I came away from chapters on less-famihar topics with a feel. ing of being well informed.
cellular membrane fusion and cell fusion. There are 12 cllapters. A strong editorial hand Is clear. Not only are all the contributions brief and to the poht (none Is longer than 22 pages) but they all share a common format, being divided Into sections entitled Introduction, Current Research and Final Comments. Hawng been involved in the study of exocytotic mechanisms for several years, I thought that by now ! would know most of the personalities in the field. Not sol It was a bit of a surprise to find that few of the authors 0ncludmg the editor) were known to me, even by reputation. This then, is not the team that I could have .~plected were I sitting in the editor's chair How well do they stand up? My impression is that the further removed the chaprers are from my own interests, the more informative and more authoritative they become. Thus, the prehminary overview by O'Day yields little useful inforn~ation abuu" [uslon processes, and he receives scant support from the other authors in this initial section. It seems to me that Knoll and Plattn~r were more concerned to re-
establish priority for their idea of the focal interacUon between fusin§ membranes than to address the frontiers of their subject. For most people, the main argument here was settled around 1980 by the work of Chandler and Heuser and, as far as I know, they were the first to use the term fusion pore. Maybe the Plattner group did get in first, and maybe there are old scores to settle, but it doesn't make for a very engrossing essay, especially coming from a group that continues to rr~'~, important contribution,. Lt,c)'s chapter is marred by careless proof reading (even to the point of misspelling his own name in the reference list). He seems to be out of touch with the most important recent developments in the field and I am not certain that he has really accepted the idea that interacting membranes undergoing fusion make contact only at very discrete 'focal' points. Altogether, th~s section is weak It needed a chapter from a theoretician - one who could explain the stability of the lipid bilayer and the energetic considerations that make contact at molecular feel.~g distance so
TRENDS IN CELL BIOLOGYVOL. 4 JANUARY 1.994
Anthony N. Corps Departmentof Cellular Physiology,AFRC Babraham InsUtute, Sabraham, Cambridge,UK CB2 4AT.
31
MISCELLANEA
gl. Do Gomperts Departmentof Physiology, UnlvemtyCollege London, Rockefeller Building, UniversityStreet, London,UK WCIE 6h
32
improbable. Even more importantly, it [,.=ededa contribution from one of the electrophysmlogists, to describe the earliest steps in the formation of the fusion pore, at the stage when its dimensions are too small to resolve by morphological methods. Indeed, the technique of whole-cell patchclamping gets hardly a mention =n this book and yet it is the practitioners in this field who have contributed more than anyone else to the understanding of membrane fusion in the last few years Intracellular processes of membrane fusion are presented with respect to some of the weU-known systems. There is an informative chapter describing exocytosls in eggs (Khne) and rather hght-weight contributions on mast cells (Koopman) and platelets (Gerard et al.). Many of the permutations and combinations of Caz*, GTP, phorbol esters, staurosporin, protein kinase C, and phosphohpases of many colours are on show here, but I didn't find much to challenge the mind. The best chapter in this section is by Anja Leyte and her colleagues from the Cell Biology Program at EMBL. In a dozen pages or so, they give an excellent resum6 of the goings on in the trons Golgl network and nearby compartments. The idea that heterotrimerlc and mono. merit GTP-blnding proteins interact to control, and then to ensure accuracy of, membrane fusion Is one that is going to be around for some time to come. Phagocytosls (Lewis, Browning and O'Day) is discussed mainly from the viewpoint of the protozoans. I get the feeling that O'Day stands here on much firmer ground than in his introductory overview. The third section, on cell fusion, commences with three chapters on myotube formation. There is Priveson the control and role of Caz*, followed by Sauro and Strickland who concentrate on phosphohpid metabolism (and CaZ*), and then David and Fitzpatrick on protein phosphorylation (with still more Ca2*). If I wanted to learn about skeletal muscle development, this book would be a useful starting point The final chapter finds O'Day (this time with Lydan) obviously on home territory with Dictyostelium. Yet again, Ca2÷ figures as an Important mediator of membrane fusion as it has for at least the last 50 (I am tempted to say 100) ye,*r;. A notable absence from the book is an account of the fusion of sperm with egg. A good description of this process could have disposed of
the idea that fusion between cells is driven by osmotic forces. It could also have killed the notion that Ca2* is an essential ingredient for the all cell-cell fusions in short, while Ca2* was needed for the readers of this journal to make their start in life, sea urchins get by without. After all this time it is remarkable how few clues we have concerning the identity of the CaZ*-bindlng proterns that mediate membrane fusion. Even more remarkable is how few authors are prepared to face up to the challenge and think about what it is that Caz* and its unidentified binding proteins might actually do. Quite clearly, although its site of action is always intracellular, its function must be quite different for intracellular
Encompassing ceils and organelles Molecular Biology of Membranes', Structure and Function by Howard R. Petty, Plenum Publishing, 1993. $.~9.50 (379 pages) ISBN 0 306 44429 1 The last few years have seen a rapid proliferation of our knowledge of the molecular basis of biological membrane function. While some of the new informal.ion has found its way into the latest edlbons of general bio. chemi~i.ly L~xts, there is clearly a need for a new comprehensive book to accompany courses on membranes for undergraduates and begmning postgraduates. Students and teachers of such courses will therefore welcome Howard Petty's book, which is prl. marily aimed at just such an audience. The book essentially consists of two halves, After a brief introduction, three chapters describe the structure and molecular assembly of lipids, carbohydrates and proteins that form the principal components of biological membranes, One chapter is devoted to electron microscopy and crystallographic methods of studying struc. ture, but spectroscopic techniques are not included. The remaining five chapters are concerned with function. The topics covered include energy transduction, transport, receptors,
fusions and extrac,llular fusions In the latter situabon the Ca2. that matters is absent from contact zones between the fusing surfaces. Thus, although Ca2. appears as a common theme almost throughout this book, linking the various systems, we should not be deluded into believing that it always plays the same game. I would have preferred to concentrate on events either on the inside or on the outside, and then to seek some of the exceptions to the rules such as Ca2*inhibited fusion, Na*-mduced fusion and cAMP-induced fusion in the three Ps (i.e Parathyroid, Pituitary and Parotid) By distancing ourselves from Caz* we might actually get a better idea of why it appears to be so good for membrane fusion.
fusion and membrane biosynthesis, while a final chapter discusses the involvement of membranes in cancer. A major impetus to membrane research over the past few years has been the increasing application of molecular genetic techniques. Although there is no specific chapter on this approach, there are numerous references to ~tthroughout the book For example, the transport chapter contains a description of Kaback's sitedirected mutagenesls experiments with lac permease, and genetic analysis of protein targeting is discussed under membrane formation, I have some reservations about the part of the book on molecular strut. tures. Undoubtedly much of the current excitement in membrane reseal~1~arises from progress towards elucidating the three-dimensional structure of membrane proteins. Unfortunately, the treatment of this key topic is not well organized, with essential material spread over several chapters. Surely the structure of the bacterial photosynthetic reaction centre, whose determination was a lan,imark in membrane research, should have appeared in the first part of the book rather than in a later chapter on bioenergetics. Furthermore, the 1975 Henderson and Unwin model of bacteriorhodopsin is presented rather than the higher-resolution 1990 model that.gives much insight into the molecular mechanism of proton pumping, The transmembrane ~-helix as a probable key structural component would benefit from more emphasis and curiously is not mentioned until after a discussion of membrane protein topology.
TRENDS IN CELLBIOLOGYVOL 4 JANUARY1994