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1.
Septins are conserved guanine nucleotide-binding proteins that polymerize into filaments at the cell cortex or in association with other cytoskeletal proteins, such as actin or microtubules. As integral players in many morphogenic and signaling events, septins form scaffolds important for the recruitment of the cytokinetic machinery, organization of the plasma membrane, and orientation of cell polarity. Mutations in septins or their misregulation are associated with numerous diseases. Despite growing appreciation for the importance of septins in different aspects of cell biology and disease, septins remain relatively poorly understood compared with other cytoskeletal proteins. Here in this review, we highlight some of the recent developments of the last two years in the field of septin cell biology. 相似文献
2.
Septins are GTP-binding proteins that form filaments and higher-order structures on the cell cortex of eukaryotic cells and associate with actin and microtubule cytoskeletal networks. When assembled, septins coordinate cell division and contribute to cell polarity maintenance and membrane remodeling. These functions manifest themselves via scaffolding of cytosolic proteins and cytoskeletal networks to specific locations on membranes and by forming diffusional barriers that restrict lateral diffusion of proteins embedded in membranes. Notably, many neurodegenerative diseases and cancers have been characterized as having misregulated septins, suggesting that their functions are relevant to diverse diseases. Despite the importance of septins, little is known about what features of the plasma membrane influence septin recruitment and alternatively, how septins influence plasma membrane properties. Septins have been localized to the cell cortex at the base of cilia, the mother-bud neck of yeast, and branch points of filamentous fungi and dendritic spines, in cleavage furrows, and in retracting membrane protrusions in mammalian cells. These sites all possess some degree of curvature and are likely composed of distinct lipid pools. Depending on the context, septins may act alone or in concert with other cytoskeletal elements to influence and sense membrane properties. The degree to which septins react to and/or induce changes in shape and lipid composition are discussed here. As septins are an essential player in basic biology and disease, understanding the interplay between septins and the plasma membrane is critical and may yield new and unexpected functions. 相似文献
3.
Neuronal morphogenesis is guided by outside-in signals and inside-out mechanisms, which require spatiotemporal precision. How the intracellular mechanisms of neuronal morphogenesis are spatiotemporally controlled is not well understood. Septins comprise a unique GTPase module, which consists of complexes with differential localizations and functions. Septins demarcate distinct membrane domains in neural precursor cells, orienting the axis of cell division and the sites of neurite formation. By controlling the localization of membrane and cytoskeletal proteins, septins promote axon-dendrite formation and polarity. Furthermore, septins modulate vesicle exocytosis at pre-synaptic terminals, and stabilize dendritic spines and post-synaptic densities in a phospho-regulatable manner. We posit that neuronal septins are topologically and functionally specialized for the spatiotemporal regulation of neuronal morphogenesis and plasticity. 相似文献
4.
Septins comprise a conserved family of proteins that are found primarily in fungi and animals. These GTP-binding proteins have several roles during cell division, cytoskeletal organization and membrane-remodelling events. One factor that is crucial for their functions is the ordered assembly of individual septins into oligomeric core complexes that, in turn, form higher-order structures such as filaments, rings and gauzes. The molecular details of these interactions and the mechanism by which septin-complex assembly is regulated have remained elusive. Recently, the first detailed structural views of the septin core have emerged, and these, along with studies of septin dynamics in vivo, have provided new insight into septin-complex assembly and septin function in vivo. 相似文献
5.
Septins comprise a eukaryotic guanine nucleotide binding protein subfamily which form filamentous heteropolymer complexes. Although mechanism of cytokinesis is diverged by species and tissues, loss of septin function results in the multinuclear phenotype in many organisms. Hence septin filaments beneath the cleavage furrow are hypothesized as a structural basis to ensure completion of cytokinesis. However, molecular mechanisms of septin assembly, disassembly and function have been elusive despite the potential importance of this ubiquitous cytoskeletal system. Meanwhile, growing evidence suggests that mammalian septins functionally or physically interact with diverse molecules such as actin, actin-binding proteins, proteins of membrane fusion machinery, Cdc42 adapter proteins, a ubiquitin-protein ligase, and phosphoinositides. Careful integration of these data may provide insights into the mechanism of mammalian septin organization and functions in cytokinesis. 相似文献
6.
7.
Septins are a family of conserved proteins that have been implicated in a variety of cellular functions involving specialized regions of the cell cortex and changes in cell shape. The biochemistry and localization of septins suggest that they form a novel cytoskeletal system or that they function as scaffolds for the assembly of signalling complexes. This article discusses septin biochemistry and septin-interacting proteins, focusing on the missing link between the structure and biochemical properties of septin proteins, and on how they function at a molecular level in processes such as cytokinesis and yeast budding. 相似文献
8.
Septins are GTPases that form filaments in fungi and animals. In addition to their original role in cell division, septins have been shown to have roles in coordinating nuclear division, membrane trafficking and organizing the cytoskeleton. Many recent studies have examined subcellular localization of septins in a wide range of fungi and animals. Septin localization shows three patterns, which generally correspond to function across kingdoms. Septins that localize to projections shape and compartmentalize emerging growth. Septins that localize to partitions compartmentalize pre-existing cellular material. Septins that localize to the whole cell are involved in membrane trafficking and organizing the cytoskeleton and are most often in animals. The difference in localization pattern frequency between kingdoms will probably disappear as more septins are examined in diverse organisms and tissues. 相似文献
9.
Septins are a family of cytoskeletal proteins involved in cytokinesis, targeting of proteins to specific sites on the plasma membrane, and cellular morphogenesis. While many aspects of their function in cytokinesis in yeast cells have been investigated, the function of septins in mammalian cells is less well understood. For example, septins are present in post-mitotic neurons, suggesting they have other roles in, for example, establishing cell polarity. The full extent of the septin gene family is not known in mammalian cells. To better understand the septin gene family, we have cloned and characterized a novel mammalian septin. 相似文献
10.
Septins are a conserved family of eukaryotic GTP-binding, filament-forming proteins. In Saccharomyces cerevisiae, five septins (Cdc3p, Cdc10p, Cdc11p, Cdc12p, and Shs1p) form a complex and colocalize to the incipient bud site and as a collar of filaments at the neck of budded cells. Septins serve as a scaffold to localize septin-associated proteins involved in diverse processes and as a barrier to diffusion of membrane-associated proteins. Little is known about the role of nucleotide binding in septin function. Here, we show that Cdc3p, Cdc10p, Cdc11p, and Cdc12p all bind GTP and that P-loop and G4 motif mutations affect nucleotide binding and result in temperature-sensitive defects in septin localization and function. Two-hybrid, in vitro, and in vivo analyses show that for all four septins nucleotide binding is important in septin-septin interactions and complex formation. In the absence of complete complexes, septins do not localize to the cortex, suggesting septin localization factors interact only with complete complexes. When both complete and partial complexes are present, septins localize to the cortex but do not form a collar, perhaps because of an inability to form filaments. We find no evidence that nucleotide binding is specifically involved in the interaction of septins with septin-associated proteins. 相似文献
11.
Eukaryotic cells develop asymmetric shapes suited for specific physiological functions. Morphogenesis of polarized domains and structures requires the amplification of molecular asymmetries by scaffold proteins and regulatory feedback loops. Small monomeric GTPases signal polarity, but how their downstream effectors and targets are spatially co-ordinated to break cell symmetry is poorly understood. Septins comprise a novel family of GTPases that polymerize into non-polar filamentous structures which scaffold and restrict protein localization. Recent studies show that septins demarcate distinct plasma membrane domains and cytoskeletal tracks, enabling the formation of intracellular asymmetries. Here, we review these findings and discuss emerging mechanisms by which septins promote cell asymmetry in fungi and animals. 相似文献
12.
Background
Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison. 相似文献13.
Septins: the fourth component of the cytoskeleton 总被引:1,自引:0,他引:1
Septins belong to a family of proteins that is highly conserved in eukaryotes and is increasingly recognized as a novel component of the cytoskeleton. All septins are GTP-binding proteins that form hetero-oligomeric complexes and higher-order structures, including filaments and rings. Recent studies have provided structural information about the different levels of septin organization; however, the crucial structural determinants and factors responsible for septin assembly remain unclear. Investigations on the molecular functions of septins have highlighted their roles as scaffolds for protein recruitment and as diffusion barriers for subcellular compartmentalization in numerous biological processes, including cell division and host-microorganism interactions. 相似文献
14.
Septins are conserved guanosine triphosphate-binding cytoskeletal proteins involved in membrane remodeling. In budding yeast, five mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1), which are essential for cytokinesis, transition during bud growth from a patch to a collar, which splits into two rings in cytokinesis and is disassembled before the next cell cycle. Cdc3, Cdc10, Cdc11, and Cdc12 form an apolar octameric rod with Cdc11 at each tip, which polymerizes into straight paired filaments. We show that Shs1 substitutes for Cdc11, resulting in octameric rods that do not polymerize into filaments but associate laterally, forming curved bundles that close into rings. In vivo, half of shs1Δ mutant cells exhibit incomplete collars and disrupted neck filaments. Importantly, different phosphomimetic mutations in Shs1 can either prevent ring formation or promote formation of a gauzelike meshwork. These results show that a single alternative terminal subunit is sufficient to confer a distinctive higher-order septin ultrastructure that can be further regulated by phosphorylation. 相似文献
15.
Role of Septin cytoskeleton in spine morphogenesis and dendrite development in neurons 总被引:4,自引:0,他引:4
Tada T Simonetta A Batterton M Kinoshita M Edbauer D Sheng M 《Current biology : CB》2007,17(20):1752-1758
Septins are GTP-binding proteins that polymerize into heteromeric filaments and form microscopic bundles or ring structures in vitro and in vivo. Because of these properties and their ability to associate with membrane, F-actin, and microtubules, septins have been generally regarded as cytoskeletal components [1, 2]. Septins are known to play roles in cytokinesis, in membrane trafficking, and as structural scaffolds; however, their function in neurons is poorly understood. Many members of the septin family, including Septin 7 (Sept7), were found by mass-spectrometry analysis of postsynaptic density (PSD) fractions of the brain [3, 4], suggesting a possible postsynaptic function of septins in neurons. We report that Sept7 is localized at the base of dendritic protrusions and at dendritic branch points in cultured hippocampal neurons--a distribution reminiscent of septin localization in the bud neck of budding yeast. Overexpression of Sept7 increased dendrite branching and the density of dendritic protrusions, whereas RNA interference (RNAi)-mediated knockdown of Sept7 led to reduced dendrite arborization and a greater proportion of immature protrusions. These data suggest that Sept7 is critical for spine morphogenesis and dendrite development during neuronal maturation. 相似文献
16.
E. A. Bukharaeva V. F. Khuzakhmetova 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2018,12(1):1-9
Septins, the cytoskeletal proteins discovered in the 1970s in budding yeast cells, are currently detected in most postmitotic cells of animals and humans. In the last decade, significant progress has been made in understanding the biochemical properties of septins and their biological functions. An increasing number of studies show that these proteins play an important role in the development and physiology of specific tissues and organs. The review surveys classification, major functions and localization of septins in the nervous system of mammals and humans. Models describing the mechanisms of the septin involvement in the neurotransmitter secretion from nerve endings and the role of septins in the pathogenesis of various neurodegenerative diseases are discussed. 相似文献
17.
Röseler S Sandrock K Bartsch I Busse A Omran H Loges NT Zieger B 《Biological chemistry》2011,392(8-9):779-781
Septins are cytoskeletal GTP-binding proteins involved in processes characterized by active membrane movement, such as cytokinesis, vesicle trafficking and exocytosis. Most septins are expressed ubiquitously, however, some septins accumulate in particular tissues. The ubiquitous SEPT11 also shows high expression levels in the central nervous system and in platelets. Here, SEPT11 is involved in vesicle trafficking and may play a role in synaptic connectivity. Interestingly, mice that harbor a homozygous Sept11 null mutation, die in utero. From day 11.5 post coitum onwards, development of homozygous embryos seems to be retarded and the embryos from day 13.5 onwards were dead. 相似文献
18.
Nakahira M Macedo JN Seraphim TV Cavalcante N Souza TA Damalio JC Reyes LF Assmann EM Alborghetti MR Garratt RC Araujo AP Zanchin NI Barbosa JA Kobarg J 《PloS one》2010,5(11):e13799
Background
Septins belong to the GTPase superclass of proteins and have been functionally implicated in cytokinesis and the maintenance of cellular morphology. They are found in all eukaryotes, except in plants. In mammals, 14 septins have been described that can be divided into four groups. It has been shown that mammalian septins can engage in homo- and heterooligomeric assemblies, in the form of filaments, which have as a basic unit a hetero-trimeric core. In addition, it has been speculated that the septin filaments may serve as scaffolds for the recruitment of additional proteins.Methodology/Principal Findings
Here, we performed yeast two-hybrid screens with human septins 1–10, which include representatives of all four septin groups. Among the interactors detected, we found predominantly other septins, confirming the tendency of septins to engage in the formation of homo- and heteropolymeric filaments.Conclusions/Significance
If we take as reference the reported arrangement of the septins 2, 6 and 7 within the heterofilament, (7-6-2-2-6-7), we note that the majority of the observed interactions respect the “group rule”, i.e. members of the same group (e.g. 6, 8, 10 and 11) can replace each other in the specific position along the heterofilament. Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group (p<0.001), SEPT3 group (p<0.001) and SEPT7 group (p<0.001). SEPT2 type septins preferentially interacted with septins of the SEPT6 group (p<0.001) aside from being the only septin group which interacted with members of its own group. Finally, septins of the SEPT3 group interacted preferentially with septins of the SEPT7 group (p<0.001). Furthermore, we found non-septin interactors which can be functionally attributed to a variety of different cellular activities, including: ubiquitin/sumoylation cycles, microtubular transport and motor activities, cell division and the cell cycle, cell motility, protein phosphorylation/signaling, endocytosis, and apoptosis. 相似文献19.
Borg/septin interactions and the assembly of mammalian septin heterodimers,trimers, and filaments 总被引:9,自引:0,他引:9
Sheffield PJ Oliver CJ Kremer BE Sheng S Shao Z Macara IG 《The Journal of biological chemistry》2003,278(5):3483-3488
Septins constitute a family of guanine nucleotide-binding proteins that were first discovered in the yeast Saccharomyces cerevisiae but are also present in many other eukaryotes. In yeast they congregate at the bud neck and are required for cell division. Their function in metazoan cells is uncertain, but they have been implicated in exocytosis and cytokinesis. Septins have been purified from cells as hetero-oligomeric filaments, but their mechanism of assembly is unknown. Further studies have been limited by the difficulty in expressing functional septin proteins in bacteria. We now show that stable, soluble septin heterodimers can be produced by co-expression from bicistronic vectors in bacteria and that the co-expression of three septins results in their assembly into filaments. Pre-assembled dimers and trimers bind guanine nucleotide and show a slow GTPase activity. The assembly of a heterodimer from monomers in vitro is accompanied by GTP hydrolysis. Borg3, a downstream effector of the Cdc42 GTPase, binds specifically to a septin heterodimer composed of Sept6 and Sept7 and to the Sept2/6/7 trimer, but not to septin monomers or to other heterodimers. Septins associate through their C-terminal coiled-coil domains, and Borg3 appears to recognize the interface between these domains in Sept6 and Sept7. 相似文献
20.
Mostowy S Janel S Forestier C Roduit C Kasas S Pizarro-Cerdá J Cossart P Lafont F 《Biophysical journal》2011,(8):1949-1959
Septins are conserved GTPases that form filaments and are required for cell division. During interphase, septin filaments associate with cellular membrane and cytoskeleton networks, yet the functional significance of these associations have, to our knowledge, remained unknown. We recently discovered that different septins, SEPT2 and SEPT11, regulate the InlB-mediated entry of Listeria monocytogenes into host cells. Here we address the role of SEPT2 and SEPT11 in the InlB-Met interactions underlying Listeria invasion to explore how septins modulate surface receptor function. We observed that differences in InlB-mediated Listeria entry correlated with differences in Met surface expression caused by septin depletion. Using atomic force microscopy on living cells, we show that septin depletion significantly reduced the unbinding force of InlB-Met interaction and the viscosity of membrane tethers at locations where the InlB-Met interaction occurs. Strikingly, the same order of difference was observed for cells in which the actin cytoskeleton was disrupted. Consistent with a proposed role of septins in association with the actin cytoskeleton, we show that cell elasticity is decreased upon septin or actin inactivation. Septins are therefore likely to participate in anchorage of the Met receptor to the actin cytoskeleton, and represent a critical determinant in surface receptor function. 相似文献