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Editorial: Nuclear pores
Seminars in Cell & Developmental Biology 68 (2017) 1
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial: Nuclear pores It was not before 1949 that we learned of the presence of gaps in the nuclear envelope of eukaryotic cells owing to an electronmicroscopy study [1]. Back then, they appeared as electron-opaque material spanning the nuclear envelope at regular distances and were proposed to account for the leakiness of the nuclear envelope. Step by step the gaps came into sharper focus. Owing to intense research our understanding of the enigmatic gaps has gradually improved and we now know a great deal more about them. It became clear that they are complex proteinaceous assemblies engaged in fundamental cell physiological processes and the term nuclear pore complex (NPCs) was established. The nuclear envelope possesses an outer and an inner nuclear membrane, facing the cytoplasm and the nucleus, respectively. Both membranes are separated by fluid-filled space termed cisterna but are joined at regular distances forming gaps in the nuclear envelope, and it is these gaps that appeared as electron-opaque material when NPCs were first discovered. In the following decades the NPC structure and composition have been resolved at the single molecule level and the beauty of this elaborate assembly has come to light. The structural makeup of the NPC forms a tapered lumen, which is narrowest at the centre of the NPC and referred to as NPC central channel, through which nucleocytoplasmic transport is mediated in a highly selective manner. The NPC is made up of multiple copies of ∼30 different proteins termed nucleoporins (Nups) that are arranged in defined subcomplexes with distinct roles. One third of Nups is rich in clusters of phenylalanine-glycine-repeats, termed FG-Nups, which exhibit a highly dynamic behaviour and impart transport selectivity to the NPC. Our understanding of NPC structure, composition and function has been substantially refined over the past decades thanks to breakthroughs in this research field which still takes centre stage in diverse biomedical research areas. In this special issue of Seminars in Cell and Developmental Biology on Nuclear Pores, we have assembled a collection of chapters which are not focused on exhaustive details and yet reflect comprehensively on NPCs from a diversity of biomedical and biophysical aspects, highlight ongoing debates and far reaching consequences of NPC research. The remarkable transport capacity and selectivity of NPCs is ascribed to FG-Nups. An individual NPC enables selective transport of up to 1000 molecules per second in a receptor-mediated manner but limits passive diffusion of unselective cargoes to a maximum molecular weight of 40 kDa. Iker Valle Aramburu and Edward Lemke provide a current overview regarding the molecular biochemical interactions between FG-Nups and receptor-cargocomplexes that enable recognition and translocation through the NPC channel. Kinetics of both import and export through NPCs is reviewed by Ulrich Kubitscheck and Jan-Peter Siebrasse based on fluorescence microscopy analysis at the single molecule and NPC http://dx.doi.org/10.1016/j.semcdb.2017.08.001 1084-9521/© 2017 Published by Elsevier Ltd.
level. The structural arrangement of FG-Nups that confer transport selectivity to NPCs is a subject of a heated debate with several models proposed as highlighted in two reviews. Yusuke Sakiyama, Radhakrishnan Panatala and Roderick Lim present the polymer brush/entropic barrier-model as a basis for the FG-Nups barrier function based on spatiotemporal investigations carried out with high-speed atomic force microscopy (AFM) on native NPCs at astonishing structural resolution and timescale approaching the transport kinetics of NPCs. George Stanley, Ariberto Fassati and Bart Hoogenboom present the hydrogel-model as a basis for the barrier function of FG-Nups based on biomechanical investigations performed with AFM at striking resolution on native individual NPCs. Another enthralling field is the elucidation of the mechanisms utilised by viruses for NPC docking and genome delivery into the nucleus reviewed by Justin Flatt and Urs Greber for a diversity of viruses. Nucleocytoplasmic transport may be the first physiological role associated with NPCs but it is certainly not the only one. Rather, NPCs are engaged in a variety of fundamental physiological activities. NPC proteins are multi-functional and play important roles in mitosis, gene expression and development highlighted in a review by Mohammed Hezwani and Birthe Fahrenkrog. NPCs also play key roles in apoptosis, a pivotal physiological process with severe pathological consequences unless kept in check. The role of NPCs in apoptosis is highlighted in a review by Victor Shahin. Based on several lines of structural evidence, a hypothesis was proposed postulating that NPCs share common evolutionary origin with other intracellular systems responsible for active management of endomembranes. A review by Ivan Liashkovich and Victor Shahin summarises the evidence supporting this hypothesis from structural and functional aspects. Martin Goldberg discusses evidence for a linkage between NPCs and microtubule network elements and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture in his review. In the light of the paramount importance of NPCs in critical physiological process it comes as no surprise that onset and progression of numerous diseases and pathologies are closely associated with NPCs malfunctions and mutations. Maximiliano D’Angelo and Stephen Sakuma provide an overview of NPCs-related diseases in their comprehensive review which includes cancer, ageing, neurodegenerative disorders and viral infections amongst many others. Finally, we thank the authors and the reviewers for their contributions and hope that this special issue will be informative, enjoyable and inspiring for the readers. Reference [1] H.G. Callan, J.T. Randall, S.G. Tomlin, An electron microscope study of the nuclear membrane, Nature 163 (1949) 280.
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial: Nuclear pores It was not before 1949 that we learned of the presence of gaps in the nuclear envelope of eukaryotic cells owing to an electronmicroscopy study [1]. Back then, they appeared as electron-opaque material spanning the nuclear envelope at regular distances and were proposed to account for the leakiness of the nuclear envelope. Step by step the gaps came into sharper focus. Owing to intense research our understanding of the enigmatic gaps has gradually improved and we now know a great deal more about them. It became clear that they are complex proteinaceous assemblies engaged in fundamental cell physiological processes and the term nuclear pore complex (NPCs) was established. The nuclear envelope possesses an outer and an inner nuclear membrane, facing the cytoplasm and the nucleus, respectively. Both membranes are separated by fluid-filled space termed cisterna but are joined at regular distances forming gaps in the nuclear envelope, and it is these gaps that appeared as electron-opaque material when NPCs were first discovered. In the following decades the NPC structure and composition have been resolved at the single molecule level and the beauty of this elaborate assembly has come to light. The structural makeup of the NPC forms a tapered lumen, which is narrowest at the centre of the NPC and referred to as NPC central channel, through which nucleocytoplasmic transport is mediated in a highly selective manner. The NPC is made up of multiple copies of ∼30 different proteins termed nucleoporins (Nups) that are arranged in defined subcomplexes with distinct roles. One third of Nups is rich in clusters of phenylalanine-glycine-repeats, termed FG-Nups, which exhibit a highly dynamic behaviour and impart transport selectivity to the NPC. Our understanding of NPC structure, composition and function has been substantially refined over the past decades thanks to breakthroughs in this research field which still takes centre stage in diverse biomedical research areas. In this special issue of Seminars in Cell and Developmental Biology on Nuclear Pores, we have assembled a collection of chapters which are not focused on exhaustive details and yet reflect comprehensively on NPCs from a diversity of biomedical and biophysical aspects, highlight ongoing debates and far reaching consequences of NPC research. The remarkable transport capacity and selectivity of NPCs is ascribed to FG-Nups. An individual NPC enables selective transport of up to 1000 molecules per second in a receptor-mediated manner but limits passive diffusion of unselective cargoes to a maximum molecular weight of 40 kDa. Iker Valle Aramburu and Edward Lemke provide a current overview regarding the molecular biochemical interactions between FG-Nups and receptor-cargocomplexes that enable recognition and translocation through the NPC channel. Kinetics of both import and export through NPCs is reviewed by Ulrich Kubitscheck and Jan-Peter Siebrasse based on fluorescence microscopy analysis at the single molecule and NPC http://dx.doi.org/10.1016/j.semcdb.2017.08.001 1084-9521/© 2017 Published by Elsevier Ltd.
level. The structural arrangement of FG-Nups that confer transport selectivity to NPCs is a subject of a heated debate with several models proposed as highlighted in two reviews. Yusuke Sakiyama, Radhakrishnan Panatala and Roderick Lim present the polymer brush/entropic barrier-model as a basis for the FG-Nups barrier function based on spatiotemporal investigations carried out with high-speed atomic force microscopy (AFM) on native NPCs at astonishing structural resolution and timescale approaching the transport kinetics of NPCs. George Stanley, Ariberto Fassati and Bart Hoogenboom present the hydrogel-model as a basis for the barrier function of FG-Nups based on biomechanical investigations performed with AFM at striking resolution on native individual NPCs. Another enthralling field is the elucidation of the mechanisms utilised by viruses for NPC docking and genome delivery into the nucleus reviewed by Justin Flatt and Urs Greber for a diversity of viruses. Nucleocytoplasmic transport may be the first physiological role associated with NPCs but it is certainly not the only one. Rather, NPCs are engaged in a variety of fundamental physiological activities. NPC proteins are multi-functional and play important roles in mitosis, gene expression and development highlighted in a review by Mohammed Hezwani and Birthe Fahrenkrog. NPCs also play key roles in apoptosis, a pivotal physiological process with severe pathological consequences unless kept in check. The role of NPCs in apoptosis is highlighted in a review by Victor Shahin. Based on several lines of structural evidence, a hypothesis was proposed postulating that NPCs share common evolutionary origin with other intracellular systems responsible for active management of endomembranes. A review by Ivan Liashkovich and Victor Shahin summarises the evidence supporting this hypothesis from structural and functional aspects. Martin Goldberg discusses evidence for a linkage between NPCs and microtubule network elements and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture in his review. In the light of the paramount importance of NPCs in critical physiological process it comes as no surprise that onset and progression of numerous diseases and pathologies are closely associated with NPCs malfunctions and mutations. Maximiliano D’Angelo and Stephen Sakuma provide an overview of NPCs-related diseases in their comprehensive review which includes cancer, ageing, neurodegenerative disorders and viral infections amongst many others. Finally, we thank the authors and the reviewers for their contributions and hope that this special issue will be informative, enjoyable and inspiring for the readers. Reference [1] H.G. Callan, J.T. Randall, S.G. Tomlin, An electron microscope study of the nuclear membrane, Nature 163 (1949) 280.