title: Deciphering the rules governing assembly order of mammalian septin complexes.
abstract: Septins are conserved GTP-binding proteins that assemble into lateral diffusion barriers and molecular scaffolds. Vertebrate genomes contain 9-17 septin genes that encode both ubiquitous and tissue-specific septins. Expressed septins may assemble in various combinations through both heterotypic and homotypic G-domain interactions. However, little is known regarding assembly states of mammalian septins and mechanisms directing ordered assembly of individual septins into heteromeric units, which is the focus of this study. Our analysis of the septin system in cells lacking or overexpressing selected septins reveals interdependencies coinciding with previously described homology subgroups. Hydrodynamic and single-particle data show that individual septins exist solely in the context of stable six- to eight-subunit core heteromers, all of which contain SEPT2 and SEPT6 subgroup members and SEPT7, while heteromers comprising more than six subunits also contain SEPT9. The combined data suggest a generic model for how the temporal order of septin assembly is homology subgroup-directed, which in turn determines the subunit arrangement of native heteromers. Because mammalian cells normally express multiple members and/or isoforms of some septin subgroups, our data also suggest that only a minor fraction of native heteromers are arranged as perfect palindromes.
authors: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden. mikael.sellin@molbiol.umu.se
authors: Mikael E
authors: ME
authors: Sellin
authors: Linda
authors: L
authors: Sandblad
authors: Sonja
authors: S
authors: Stenmark
authors: Martin
authors: M
authors: Gullberg
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058112:Septins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; C000602252:SEPTIN2 protein, human; C113158:SEPTIN7 protein, human; C474315:SEPTIN9 protein, human; D058112:Septins