- Email: [email protected]
The ESCRT machinery: When function follows form
G Model
ARTICLE IN PRESS
YSCDB-2445; No. of Pages 3
Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
The ESCRT machinery: When function follows form
From bacteria to humans, the ability of cells to divide, compartmentalize and exert different functions is critically dependent on their capacity to remodel their internal and external membranes. In this context, both lipid- and protein-based mechanisms are important for the regulation of membrane curvature. Cellular membranes can be curved either positively – towards the cytoplasm, or negatively – away from it. The generation of positive membrane curvature allows notably releasing membrane-bound vesicles into the cytoplasmic space. The analysis of two major processes that require the formation of intracellular vesicular carriers, clathrinmediated endocytosis and COPI/II-dependent ER/Golgi transport, have revealed that positive membrane curvature can, among other mechanisms, be generated by the local assembly of scaffolds of curvature-generating proteins on the cytoplasmic leaflet of the plasma membrane. Following vesicle release into the cytoplasm, protein coats are disassembled again and their individual components can be recycled for further use. A well-known example of a biological process involving the generation of negative membrane curvature is the biogenesis of Multi-Vesicular Endosomes (MVE). During MVE formation, a bending of the limiting membrane of the endosome away from the cytoplasm results in the release of so-called Intra-Lumenal Vesicles (ILV) into the organelle lumen. While the bending of endosomal membranes during this process could, in principle, also be achieved through the assembly of a protein coat on the cytoplasmic side of the endosomal membrane, such a process would be extremely costly for the cell: Indeed, in this topology curvature-generating coat proteins would ultimately be sequestered away and lost in the ILV lumen. How endosomal membranes are deformed during ILV formation remained therefore a longstanding mystery. The discovery of the Endosomal Sorting Complex Required for Transport (ESCRT) by the lab of Scott Emr provided an answer to this enigma [1–5]. By performing pioneering genetic screens in yeast, the Emr lab was indeed able to identify an evolutionarily conserved membrane trafficking machinery of around 30 proteins that assemble into 5 functional subcomplexes. Upon recognition of endocytosed molecules by the ESCRT-0 complex, ESCRT-I & -II act to sequester the endocytic cargo in endosomal microdomains that prefigure the membrane of the future ILV. The components of the ESCRT-III subcomplex then polymerize into spiral-shaped filaments that are tightly associated with the endosomal membrane. Through a mechanism that is the subject of intensive investigations, filament polymerization ultimately generates a conical three-dimensional helix that points towards the lumen of the
organelle and constricts the endosomal membrane at the bud neck of the nascent ILV. Finally, the catalytic activity of the ATPhydrolyzing Vps4 complex promotes membrane scission and/or disassembly of the ESCRT machinery. Of particular importance, the topology of the ESCRT machinery, which results in the apposition of the membrane-deforming helix to the cytoplasmic side of the vesicle neck, allows the cytoplasmic release and subsequent reuse of ESCRT proteins once a cycle of ILV biogenesis has been completed. While the generation of the ILVs of MVEs is one important process that involves the bending of cellular membranes away from the cytoplasm, it is in no way the only one. At the level of the plasma membrane, a topologically similar event is the budding of enveloped viruses from the cell surface. Accordingly, it soon became obvious that several ESCRT proteins can be coopted to promote the release of HIV and other viruses. Importantly, a number of recent studies have revealed that, beyond the pathological context of viral infection, ESCRTs can also act to promote cell surface budding under normal, physiological conditions. This allows to trigger the release of extracellular vesicles involved in cell communication or to discard damaged fragments of the plasma membrane. A further site of ESCRT action is the cytoplasmic bridge between mitotic sister cells, where ESCRT proteins act to promote cytokinetic abscission. In the light of these findings, the ESCRT machinery appears as a major membrane remodeling machinery that is deployed in different biological contexts to generate and cleave membrane stalks that point away from the cell body. Through a series of seven review articles, the present issue of Seminars in Cell and Developmental Biology aims to provide an extensive, although necessarily not comprehensive, overview of our current understanding of the molecular activity and the physiological functions of the ESCRT machinery. In addition to providing a current state of the art, the contributing authors identify a number of important open issues that will be of major interest for future research. Throughout the two decades that followed the initial discovery of the ESCRT machinery, major efforts have been undertaken to understand how ESCRT components interact with endosomal membranes and endocytosed material to promote the incorporation of specific cargo into ILVs. Frankel and Audhya [6] present our current knowledge of these processes with a particular emphasis on the mechanisms that ensure the recognition of endocytic cargo and its transfer to ILVs. In addition to the major importance of Ubiquitin marks for ESCRT-mediated cargo sorting, a number of studies have revealed the existence of additional, ESCRT-dependent but
https://doi.org/10.1016/j.semcdb.2017.11.003 1084-9521/© 2017 Published by Elsevier Ltd.
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003
G Model YSCDB-2445; No. of Pages 3 2
ARTICLE IN PRESS Editorial / Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
Ubiquitin-independent ILV sorting pathways. As our understanding of ESCRT-dependent membrane remodeling increases, a major challenge for the future will be to generate models of ESCRT function that take into account both the biochemical interactions that govern cargo recognition and transfer, as well as the membrane biophysics of ILV biogenesis. Studies of the endocytic trafficking of transmembrane growth factor receptors, most prominently the EGF receptor, revealed that the incorporation of receptors into the ILVs of MVEs can have a major impact on cell signaling. Szymanska et al. review our current knowledge of the importance of ESCRT-dependent ILV sorting for the endosomal regulation of cellular signaling pathways [7]. While ESCRT activity is required to inhibit ligand-induced or ligandindependent signaling by some receptors, other pathways depend on ESCRT function for the control of receptor levels at the cell surface or the activation of downstream signal transduction. While the ESCRT machinery was initially identified through its function in the endocytic sorting of membrane-anchored molecules, a growing number of studies suggest that in selected cases, the ESCRT-dependent sorting of cytoplasmic factors to the ILV lumen can sequester away positive or negative regulators of cell signaling. An important issue for the years to come will be to determine how the sequestration of these cytoplasmic regulators in endosomal ILVs contributes to the regulation of different cellular signaling pathways in vivo. The ESCRT-dependent incorporation of signaling molecules into the ILVs of MVEs is often a prerequisite for their subsequent lysosomal degradation. Alternatively, different cellular substrates ranging from specific molecules to entire organelles can be degraded through autophagy. Lefebvre et al. highlight the importance of the ESCRT machinery for the execution of different autophagy programs [8]. Endosomal microautophagy involves the ESCRT-dependent sequestration of cytoplasmic material in the ILVs of MVEs to ensure its further lysosomal degradation. During macroautophagy, cellular material is progressively enclosed by an autophagosomal double membrane. ESCRT function is required for the fusion of autophagosomes with MVEs to generate so-called amphisomes that are competent for further fusion with lysosomes. It remains to be established whether ESCRT proteins contribute to this process by promoting the sealing of the autophagosomal membrane (a process topologically equivalent to other ESCRT functions) or through more unconventional functions in vesicle tethering or fusion. Biochemical reconstitutions and cell culture have provided invaluable mechanistic insights into ESCRT activity. Horner et al. discuss current efforts to further study the physiological functions of the ESCRT machinery in vivo, in the context of the development of a wide variety of different organisms, ranging from unicellular fungi, to plants and higher vertebrates [9]. In the light of the key role of the endo-lysosomal system in cellular information processing, it comes as no surprise that both organismal responses to environmental stimuli as well as the regulation of the amplitude and duration of developmental signals are critically dependent on ESCRT function. At the present date, the majority of developmental phenotypes that result from ESCRT dysfunctions have been suggested to originate from alterations in the endosomal regulation of cell signaling. As more and more ESCRT functions are discovered ex vivo, it will be important to address the importance of ESCRT proteins for processes such as cytokinesis, membrane repair and extracellular vesicle release in vivo. Sadoul et al. illustrate how the multiple activities of the ESCRT machinery can contribute to the development and function of the nervous system [10]. Through their ability to regulate cellular processes that range from cell survival and growth factor signaling to axonal pathfinding and remodeling as well as the control of synaptic architecture and activity, ESCRT proteins have been shown to be
implicated in a many different aspects of neural development and function. The importance of the ESCRT machinery for the integrity of the nervous system is further underscored by the finding that ESCRT mutations have been associated with severe neurodegenerative diseases in humans. In the light of the plethora of activities exerted by the ESCRT machinery, it will be a major challenge for the coming years to identify the precise cellular processes that are responsible for the dysfunctions of the nervous system that are observed in ESCRT-deficient animals. In spite of the fact that the ESCRT machinery was initially discovered due to its essential role in endo-lysosomal trafficking, evolutionary considerations suggest that the control of endosomal biogenesis may not represent the ancestral ESCRT function. Studies in Archaebacteria, which are devoid of endosomal organelles, indeed reveal the existence of archeal ESCRT proteins that control membrane curvature and scission in mitosis. Stoten and Carlton [11] discuss the regulation and function of the ESCRT machinery during cell division. While it is by now well established that ESCRT-dependent membrane scission is essential for cytokinetic abscission, a number of recent studies have started to uncover additional novel functions of the ESCRT machinery in the resealing of the nuclear membrane during mitosis or the quality control of nuclear pore complexes. A particularly interesting feature of these studies of mitotic ESCRT functions is that they have started to identify cell cycle-dependent mechanisms that allow to ensure spatio-temporal regulations of ESCRT activity. The budding of ILVs into the endosomal lumen is topologically equivalent to the release of vesicles into the extracellular space. Juan and Fürthauer describe the importance of the ESCRT machinery for the biogenesis and function of extracellular vesicles that originate through the fusion of secretory MVEs with the plasma membrane (i.e. exosomes) or through virus-like cell surface budding [12]. Despite the fact that the study of extracellular vesicles is still in its infancy, a number of studies suggest that ESCRTdependent extracellular vesicles are essential for inter-cellular and inter-organismal communication under both physiological and pathological conditions. While the standard model of ESCRTdependent ILV formation postulates that ESCRT proteins would be released into the cytoplasm following vesicle scission for subsequent reuse, a number of ESCRTs have been shown to be present in extracellular vesicles. At the present state, it is not clear whether this incorporation of ESCRTs into nascent vesicles reflects a leakiness in the regulation of ESCRT recycling during vesicular biogenesis, or a context-specific adaptation of the mechanisms that govern the ESCRT-dependent constriction and scission of vesicular membrane stalks. The advent of developmental genetics revealed that a relatively small number of genetic pathways is repeatedly used throughout evolution to generate strikingly different organisms. Similarly, the ESCRT machinery has emerged as a major cellular toolkit to perform a certain type of membrane remodeling events in a large number of, seemingly very different, biological contexts. As the ESCRT machinery is about to leave its teens, the ever increasing number of ESCRT-functions provides a highly stimulating research playground for the years to come.
References [1] D.J. Katzmann, C.J. Stefan, M. Babst, S.D. Emr, Vps27 recruits ESCRT machinery to endosomes during MVB sorting, J. Cell Biol. 162 (3) (2003) 413–423. [2] M. Babst, D.J. Katzmann, E.J. Estepa-Sabal, T. Meerloo, S.D. Emr, Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting, Dev. Cell 3 (2) (2002) 271–282. [3] M. Babst, D.J. Katzmann, W.B. Snyder, B. Wendland, S.D. Emr, Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body, Dev. Cell 3 (2) (2002) 283–289.
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003
G Model YSCDB-2445; No. of Pages 3
ARTICLE IN PRESS Editorial / Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
[4] D.J. Katzmann, M. Babst, S.D. Emr, Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I, Cell 106 (2) (2001) 145–155. [5] M. Babst, B. Wendland, E.J. Estepa, S.D. Emr, The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function, EMBO J. 17 (11) (1998) 2982–2993. [6] E.B. Frankel, A. Audhya, ESCRT-dependent cargo sorting at multivesicular endosomes, Semin. Cell Dev. Biol. (2017). [7] E. Szymanska, N. Budick-Harmelin, M. Miaczynska, Endosomal sort of signaling control: the role of ESCRT machinery in regulation of receptor-mediated signaling pathways, Semin. Cell Dev. Biol. (2017). [8] C. Lefebvre, R. Legouis, E. Culetto, ESCRT and autophagies: endosomal functions and beyond, Semin. Cell Dev. Biol. (2017). [9] D. Horner, M. Pasini, M. Beltrame, V. Madtrodonato, E. Morelli, T. Vaccari, ESCRT genes and regulation of developmental signaling, Semin. Cell Dev. Biol. (2017).
3
[10] R. Sadoul, M.H. Laporte, R. Chassefeyre, Y. Goldberg, C. Chatellard, F.J. Hemming, S. Fraboulet, The role of ESCRT during development and functioning of the nervous system, Semin. Cell Dev. Biol. (2017). [11] C. Stoten, J. Carlton, ESCRT-dependent control of membrane remodelling during cell division, Semin. Cell Dev. Biol. (2017). [12] T. Juan, M. Fürthauer, Biogenesis and function of ESCRT-dependent extracellular vesicles, Semin. Cell Dev. Biol. (2017).
Maximilian Fürthauer E-mail address: [email protected] Available online xxx
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003
ARTICLE IN PRESS
YSCDB-2445; No. of Pages 3
Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
The ESCRT machinery: When function follows form
From bacteria to humans, the ability of cells to divide, compartmentalize and exert different functions is critically dependent on their capacity to remodel their internal and external membranes. In this context, both lipid- and protein-based mechanisms are important for the regulation of membrane curvature. Cellular membranes can be curved either positively – towards the cytoplasm, or negatively – away from it. The generation of positive membrane curvature allows notably releasing membrane-bound vesicles into the cytoplasmic space. The analysis of two major processes that require the formation of intracellular vesicular carriers, clathrinmediated endocytosis and COPI/II-dependent ER/Golgi transport, have revealed that positive membrane curvature can, among other mechanisms, be generated by the local assembly of scaffolds of curvature-generating proteins on the cytoplasmic leaflet of the plasma membrane. Following vesicle release into the cytoplasm, protein coats are disassembled again and their individual components can be recycled for further use. A well-known example of a biological process involving the generation of negative membrane curvature is the biogenesis of Multi-Vesicular Endosomes (MVE). During MVE formation, a bending of the limiting membrane of the endosome away from the cytoplasm results in the release of so-called Intra-Lumenal Vesicles (ILV) into the organelle lumen. While the bending of endosomal membranes during this process could, in principle, also be achieved through the assembly of a protein coat on the cytoplasmic side of the endosomal membrane, such a process would be extremely costly for the cell: Indeed, in this topology curvature-generating coat proteins would ultimately be sequestered away and lost in the ILV lumen. How endosomal membranes are deformed during ILV formation remained therefore a longstanding mystery. The discovery of the Endosomal Sorting Complex Required for Transport (ESCRT) by the lab of Scott Emr provided an answer to this enigma [1–5]. By performing pioneering genetic screens in yeast, the Emr lab was indeed able to identify an evolutionarily conserved membrane trafficking machinery of around 30 proteins that assemble into 5 functional subcomplexes. Upon recognition of endocytosed molecules by the ESCRT-0 complex, ESCRT-I & -II act to sequester the endocytic cargo in endosomal microdomains that prefigure the membrane of the future ILV. The components of the ESCRT-III subcomplex then polymerize into spiral-shaped filaments that are tightly associated with the endosomal membrane. Through a mechanism that is the subject of intensive investigations, filament polymerization ultimately generates a conical three-dimensional helix that points towards the lumen of the
organelle and constricts the endosomal membrane at the bud neck of the nascent ILV. Finally, the catalytic activity of the ATPhydrolyzing Vps4 complex promotes membrane scission and/or disassembly of the ESCRT machinery. Of particular importance, the topology of the ESCRT machinery, which results in the apposition of the membrane-deforming helix to the cytoplasmic side of the vesicle neck, allows the cytoplasmic release and subsequent reuse of ESCRT proteins once a cycle of ILV biogenesis has been completed. While the generation of the ILVs of MVEs is one important process that involves the bending of cellular membranes away from the cytoplasm, it is in no way the only one. At the level of the plasma membrane, a topologically similar event is the budding of enveloped viruses from the cell surface. Accordingly, it soon became obvious that several ESCRT proteins can be coopted to promote the release of HIV and other viruses. Importantly, a number of recent studies have revealed that, beyond the pathological context of viral infection, ESCRTs can also act to promote cell surface budding under normal, physiological conditions. This allows to trigger the release of extracellular vesicles involved in cell communication or to discard damaged fragments of the plasma membrane. A further site of ESCRT action is the cytoplasmic bridge between mitotic sister cells, where ESCRT proteins act to promote cytokinetic abscission. In the light of these findings, the ESCRT machinery appears as a major membrane remodeling machinery that is deployed in different biological contexts to generate and cleave membrane stalks that point away from the cell body. Through a series of seven review articles, the present issue of Seminars in Cell and Developmental Biology aims to provide an extensive, although necessarily not comprehensive, overview of our current understanding of the molecular activity and the physiological functions of the ESCRT machinery. In addition to providing a current state of the art, the contributing authors identify a number of important open issues that will be of major interest for future research. Throughout the two decades that followed the initial discovery of the ESCRT machinery, major efforts have been undertaken to understand how ESCRT components interact with endosomal membranes and endocytosed material to promote the incorporation of specific cargo into ILVs. Frankel and Audhya [6] present our current knowledge of these processes with a particular emphasis on the mechanisms that ensure the recognition of endocytic cargo and its transfer to ILVs. In addition to the major importance of Ubiquitin marks for ESCRT-mediated cargo sorting, a number of studies have revealed the existence of additional, ESCRT-dependent but
https://doi.org/10.1016/j.semcdb.2017.11.003 1084-9521/© 2017 Published by Elsevier Ltd.
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003
G Model YSCDB-2445; No. of Pages 3 2
ARTICLE IN PRESS Editorial / Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
Ubiquitin-independent ILV sorting pathways. As our understanding of ESCRT-dependent membrane remodeling increases, a major challenge for the future will be to generate models of ESCRT function that take into account both the biochemical interactions that govern cargo recognition and transfer, as well as the membrane biophysics of ILV biogenesis. Studies of the endocytic trafficking of transmembrane growth factor receptors, most prominently the EGF receptor, revealed that the incorporation of receptors into the ILVs of MVEs can have a major impact on cell signaling. Szymanska et al. review our current knowledge of the importance of ESCRT-dependent ILV sorting for the endosomal regulation of cellular signaling pathways [7]. While ESCRT activity is required to inhibit ligand-induced or ligandindependent signaling by some receptors, other pathways depend on ESCRT function for the control of receptor levels at the cell surface or the activation of downstream signal transduction. While the ESCRT machinery was initially identified through its function in the endocytic sorting of membrane-anchored molecules, a growing number of studies suggest that in selected cases, the ESCRT-dependent sorting of cytoplasmic factors to the ILV lumen can sequester away positive or negative regulators of cell signaling. An important issue for the years to come will be to determine how the sequestration of these cytoplasmic regulators in endosomal ILVs contributes to the regulation of different cellular signaling pathways in vivo. The ESCRT-dependent incorporation of signaling molecules into the ILVs of MVEs is often a prerequisite for their subsequent lysosomal degradation. Alternatively, different cellular substrates ranging from specific molecules to entire organelles can be degraded through autophagy. Lefebvre et al. highlight the importance of the ESCRT machinery for the execution of different autophagy programs [8]. Endosomal microautophagy involves the ESCRT-dependent sequestration of cytoplasmic material in the ILVs of MVEs to ensure its further lysosomal degradation. During macroautophagy, cellular material is progressively enclosed by an autophagosomal double membrane. ESCRT function is required for the fusion of autophagosomes with MVEs to generate so-called amphisomes that are competent for further fusion with lysosomes. It remains to be established whether ESCRT proteins contribute to this process by promoting the sealing of the autophagosomal membrane (a process topologically equivalent to other ESCRT functions) or through more unconventional functions in vesicle tethering or fusion. Biochemical reconstitutions and cell culture have provided invaluable mechanistic insights into ESCRT activity. Horner et al. discuss current efforts to further study the physiological functions of the ESCRT machinery in vivo, in the context of the development of a wide variety of different organisms, ranging from unicellular fungi, to plants and higher vertebrates [9]. In the light of the key role of the endo-lysosomal system in cellular information processing, it comes as no surprise that both organismal responses to environmental stimuli as well as the regulation of the amplitude and duration of developmental signals are critically dependent on ESCRT function. At the present date, the majority of developmental phenotypes that result from ESCRT dysfunctions have been suggested to originate from alterations in the endosomal regulation of cell signaling. As more and more ESCRT functions are discovered ex vivo, it will be important to address the importance of ESCRT proteins for processes such as cytokinesis, membrane repair and extracellular vesicle release in vivo. Sadoul et al. illustrate how the multiple activities of the ESCRT machinery can contribute to the development and function of the nervous system [10]. Through their ability to regulate cellular processes that range from cell survival and growth factor signaling to axonal pathfinding and remodeling as well as the control of synaptic architecture and activity, ESCRT proteins have been shown to be
implicated in a many different aspects of neural development and function. The importance of the ESCRT machinery for the integrity of the nervous system is further underscored by the finding that ESCRT mutations have been associated with severe neurodegenerative diseases in humans. In the light of the plethora of activities exerted by the ESCRT machinery, it will be a major challenge for the coming years to identify the precise cellular processes that are responsible for the dysfunctions of the nervous system that are observed in ESCRT-deficient animals. In spite of the fact that the ESCRT machinery was initially discovered due to its essential role in endo-lysosomal trafficking, evolutionary considerations suggest that the control of endosomal biogenesis may not represent the ancestral ESCRT function. Studies in Archaebacteria, which are devoid of endosomal organelles, indeed reveal the existence of archeal ESCRT proteins that control membrane curvature and scission in mitosis. Stoten and Carlton [11] discuss the regulation and function of the ESCRT machinery during cell division. While it is by now well established that ESCRT-dependent membrane scission is essential for cytokinetic abscission, a number of recent studies have started to uncover additional novel functions of the ESCRT machinery in the resealing of the nuclear membrane during mitosis or the quality control of nuclear pore complexes. A particularly interesting feature of these studies of mitotic ESCRT functions is that they have started to identify cell cycle-dependent mechanisms that allow to ensure spatio-temporal regulations of ESCRT activity. The budding of ILVs into the endosomal lumen is topologically equivalent to the release of vesicles into the extracellular space. Juan and Fürthauer describe the importance of the ESCRT machinery for the biogenesis and function of extracellular vesicles that originate through the fusion of secretory MVEs with the plasma membrane (i.e. exosomes) or through virus-like cell surface budding [12]. Despite the fact that the study of extracellular vesicles is still in its infancy, a number of studies suggest that ESCRTdependent extracellular vesicles are essential for inter-cellular and inter-organismal communication under both physiological and pathological conditions. While the standard model of ESCRTdependent ILV formation postulates that ESCRT proteins would be released into the cytoplasm following vesicle scission for subsequent reuse, a number of ESCRTs have been shown to be present in extracellular vesicles. At the present state, it is not clear whether this incorporation of ESCRTs into nascent vesicles reflects a leakiness in the regulation of ESCRT recycling during vesicular biogenesis, or a context-specific adaptation of the mechanisms that govern the ESCRT-dependent constriction and scission of vesicular membrane stalks. The advent of developmental genetics revealed that a relatively small number of genetic pathways is repeatedly used throughout evolution to generate strikingly different organisms. Similarly, the ESCRT machinery has emerged as a major cellular toolkit to perform a certain type of membrane remodeling events in a large number of, seemingly very different, biological contexts. As the ESCRT machinery is about to leave its teens, the ever increasing number of ESCRT-functions provides a highly stimulating research playground for the years to come.
References [1] D.J. Katzmann, C.J. Stefan, M. Babst, S.D. Emr, Vps27 recruits ESCRT machinery to endosomes during MVB sorting, J. Cell Biol. 162 (3) (2003) 413–423. [2] M. Babst, D.J. Katzmann, E.J. Estepa-Sabal, T. Meerloo, S.D. Emr, Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting, Dev. Cell 3 (2) (2002) 271–282. [3] M. Babst, D.J. Katzmann, W.B. Snyder, B. Wendland, S.D. Emr, Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body, Dev. Cell 3 (2) (2002) 283–289.
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003
G Model YSCDB-2445; No. of Pages 3
ARTICLE IN PRESS Editorial / Seminars in Cell & Developmental Biology xxx (2017) xxx–xxx
[4] D.J. Katzmann, M. Babst, S.D. Emr, Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I, Cell 106 (2) (2001) 145–155. [5] M. Babst, B. Wendland, E.J. Estepa, S.D. Emr, The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function, EMBO J. 17 (11) (1998) 2982–2993. [6] E.B. Frankel, A. Audhya, ESCRT-dependent cargo sorting at multivesicular endosomes, Semin. Cell Dev. Biol. (2017). [7] E. Szymanska, N. Budick-Harmelin, M. Miaczynska, Endosomal sort of signaling control: the role of ESCRT machinery in regulation of receptor-mediated signaling pathways, Semin. Cell Dev. Biol. (2017). [8] C. Lefebvre, R. Legouis, E. Culetto, ESCRT and autophagies: endosomal functions and beyond, Semin. Cell Dev. Biol. (2017). [9] D. Horner, M. Pasini, M. Beltrame, V. Madtrodonato, E. Morelli, T. Vaccari, ESCRT genes and regulation of developmental signaling, Semin. Cell Dev. Biol. (2017).
3
[10] R. Sadoul, M.H. Laporte, R. Chassefeyre, Y. Goldberg, C. Chatellard, F.J. Hemming, S. Fraboulet, The role of ESCRT during development and functioning of the nervous system, Semin. Cell Dev. Biol. (2017). [11] C. Stoten, J. Carlton, ESCRT-dependent control of membrane remodelling during cell division, Semin. Cell Dev. Biol. (2017). [12] T. Juan, M. Fürthauer, Biogenesis and function of ESCRT-dependent extracellular vesicles, Semin. Cell Dev. Biol. (2017).
Maximilian Fürthauer E-mail address: [email protected] Available online xxx
Please cite this article in press as: M. Fürthauer, The ESCRT machinery: When function follows form, Semin Cell Dev Biol (2017), https://doi.org/10.1016/j.semcdb.2017.11.003