Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:020040 (SEPT3)
 17 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Septins are a family of conserved cytoskeletal GTPase forming heteropolymeric filamentous structure in interphase cells, however, the mechanism of assembly are largely unknown. Here we described the characterization of SEPT12, sharing closest homology to SEPT3 and SEPT9. It was revealed that subcellular localization of SEPT12 varied at interphase and mitotic phase. While SEPT12 formed filamentous structures at interphase, it was localized to the central spindle and to midbody during anaphase and cytokinesis, respectively. In addition, we found that SEPT12 can interact with SEPT6 in vitro and in vivo, and this interaction was independent of the coiled coil domain of SEPT6. Further, co-expression of SEPT12 altered the filamentous structure of SEPT6 in Hela cells. Therefore, our result showed that the interaction between different septins may affect the septin filament structure.
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PMID:SEPT12 interacts with SEPT6 and this interaction alters the filament structure of SEPT6 in Hela cells. 1804 94

Septins are GTPases that form heteromeric complexes and are linked to neurological disorders. Although several septin subcomplexes have been reported in various mammalian tissues, the cellular and subcellular distribution of these complexes is largely unexplored. Using antibodies against ten mammalian septins, we show that septins diverge with respect to their tissue distribution implying that septin complexes in various tissues have unique composition. Although all ten septins examined were expressed in brain tissue, we describe septin complex(es) including SEPT3, SEPT5, SEPT6, SEPT7 and SEPT11 that could be functional within the presynapse because, unlike other septins they: (1) showed an increase in expression from embryonic day 15 to post-natal day 70, (2) were abundantly expressed in axons and growth cones of developing hippocampal neurons, (3) were found in presynaptic terminals of mature synapses, (4) were enriched in a preparation of synaptic vesicles and (5) immunoprecipitated together from brain tissue and cultured nerve cells. Knockdown of SEPT5 or SEPT7 in developing hippocampal neurons impaired axon growth. Because septins are functionally linked to the cytoskeleton and vesicle traffic, presynaptic neuronal septin complexes could be important for ensuring proper axon development and neurotransmitter release.
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PMID:Characterization of presynaptic septin complexes in mammalian hippocampal neurons. 2176 34

Septins are GTP-binding and membrane-interacting proteins with a highly conserved domain structure involved in various cellular processes, including cytoskeleton organization, cytokinesis, and membrane dynamics. To date, 13 different septin genes have been identified in mammals (SEPT1 to SEPT12 and SEPT14), which can be classified into four distinct subgroups based on the sequence homology of their domain structure (SEPT2, SEPT3, SEPT6, and SEPT7 subgroup). The family members of these subgroups have a strong affinity for other septins and form apolar tri-, hexa-, or octameric complexes consisting of multiple septin polypeptides. The first characterized core complex is the hetero-trimer SEPT2-6-7. Within these complexes single septins can be exchanged in a subgroup-specific manner. Hexamers contain SEPT2 and SEPT6 subgroup members and SEPT7 in two copies each whereas the octamers additionally comprise two SEPT9 subgroup septins. The various isoforms seem to determine the function and regulation of the septin complex. Septins self-assemble into higher-order structures, including filaments and rings in orders, which are typical for different cell types. Misregulation of septins leads to human diseases such as neurodegenerative and bleeding disorders. In non-dividing cells such as neuronal tissue and platelets septins have been associated with exocytosis. However, many mechanistic details and roles attributed to septins are poorly understood. We describe here some important mammalian septin interactions with a special focus on the clinically relevant septin interactions.
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PMID:The Mammalian Septin Interactome. 2822 24

Septins are cytoskeletal proteins that assemble into nonpolar filaments. They are critical in diverse cellular functions, acting as scaffolds for protein recruitment and as diffusion barriers for subcellular compartmentalization. Human septins are encoded by 13 different genes and are classified into four groups based on sequence homology (SEPT2, SEPT3, SEPT6, and SEPT7 groups). In yeast, septins were among the first proteins reported to be modified by SUMOylation, a ubiquitin-like posttranslational modification. However, whether human septins could be modified by small ubiquitin-like modifiers (SUMOs) and what roles this modification may have in septin function remains unknown. In this study, we first show that septins from all four human septin groups can be covalently modified by SUMOs. We show in particular that endogenous SEPT7 is constitutively SUMOylated during the cell cycle. We then map SUMOylation sites to the C-terminal domain of septins belonging to the SEPT6 and SEPT7 groups and to the N-terminal domain of septins from the SEPT3 group. We finally demonstrate that expression of non-SUMOylatable septin variants from the SEPT6 and SEPT7 groups leads to aberrant septin bundle formation and defects in cytokinesis after furrow ingression. Altogether, our results demonstrate a pivotal role for SUMOylation in septin filament bundling and cell division.
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PMID:SUMOylation of human septins is critical for septin filament bundling and cytokinesis. 2905 Dec 66

The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.
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PMID:Molecular Recognition at Septin Interfaces: The Switches Hold the Key. 3291 Sep 69

The septins are filament-forming proteins found in diverse eukaryotes from fungi to vertebrates, with roles in cytokinesis, shaping of membranes and modifying cytoskeletal organization. These GTPases assemble into rod-shaped soluble hetero-hexamers and hetero-octamers in mammals, which polymerize into filaments and higher order structures. While the cell biology and pathobiology of septins are advancing rapidly, mechanistic study of the mammalian septins is limited by a lack of recombinant hetero-octamer materials. We describe here the production and characterization of a recombinant mammalian septin hetero-octamer of defined stoichiometry, the SEPT2/SEPT6/SEPT7/SEPT3 complex. Using a fluorescent protein fusion to the complex, we observed filaments assembled from this complex. In addition, we used this novel tool to resolve recent questions regarding the organization of the soluble septin complex. Biochemical characterization of a SEPT3 truncation that disrupts SEPT3-SEPT3 interactions is consistent with SEPT3 occupying a central position in the complex while the SEPT2 subunits are at the ends of the rod-shaped octameric complexes. Consistent with SEPT2 being on the complex ends, we find that our purified SEPT2/SEPT6/SEPT7/SEPT3 hetero-octamer copolymerizes into mixed filaments with separately purified SEPT2/SEPT6/SEPT7 hetero-hexamer. We expect this new recombinant production approach to lay essential groundwork for future studies into mammalian septin mechanism and function.
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PMID:Production and analysis of a mammalian septin hetero-octamer complex. 3318 30