Abstract
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.
Highlights
Septins (SEPTs) have been originally discovered in Saccharomyces cerevisiae as a family of proteins associated with cytokinesis and cell morphology
The GTPase domain (G-domain) itself has a mixed αhelix/β-sheet secondary-structure and contains three motifs: G1 (GxxxxGK[s/T]) is characterized by the presence of the phosphate-binding loop (P-loop) and is capable of interacting with nucleotide phosphate groups. Both G3 (DxxG) and G4 are directly associated with GTP binding (Sirajuddin et al, 2009). Based on their sequence homology and the number of coiled-coil domains, mammalian septins can be subdivided into four different groups termed according to their founding member SEPT2, SEPT3, SEPT6, or SEPT7 (Figure 1B)
Unlike RAS-like GTP-binding proteins the septins can assemble into multimeric complexes including two or more subunits depending on the organism (Field et al, 1996; John et al, 2007; Sellin et al, 2011a)
Summary
Septins (SEPTs) have been originally discovered in Saccharomyces cerevisiae as a family of proteins associated with cytokinesis and cell morphology. Unlike RAS-like GTP-binding proteins the septins can assemble into multimeric complexes including two or more subunits depending on the organism (Field et al, 1996; John et al, 2007; Sellin et al, 2011a). Some septins interact with proteins (CENPE/F, SNX6), which are associated with intracellular trafficking and exocytosis or are part of the kinetochore via coiled-coil domains (Nakahira et al, 2010) (Table 1).
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