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

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

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