title: Cell type-specific expression of SEPT3-homology subgroup members controls the subunit number of heteromeric septin complexes.
abstract: Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer and heterooctamer complexes, which serve as building blocks for apolar filamentous structures that differ among cell types. To determine how tissue-specific septin paralogue expression may shape core heteromer repertoires and thereby modulate properties of septin filaments, we devised protocols to analyze native septin heteromers with distinct numbers of subunits. Our evidence based on genetically manipulated human cells supports and extends recent concepts of homology subgroup-restricted assembly into distinct categories of apolar heterohexamers and heterooctamers. We also identify a category of tetramers that have a subunit composition equivalent to an octameric building block. These atypical tetramers are prevalent in lymphocytes and neural tissues, in which octamers are abundant but hexamers are rare. Our results can be explained by tissue-specific expression of SEPT3 subgroup members: SEPT3, SEPT9, and SEPT12. These serve as cognate subunits in either heterooctamers or atypical tetramers but exhibit different preferences in various tissues. The identified tissue-specific repertoires of septin heteromers provide insights into how higher-order septin structures with differential properties and stabilities may form in diverse animal cell types.
authors.affiliation: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, SwedenInstitute of Microbiology, D-BIOL, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Mikael E
authors.initials: ME
authors.lastname: Sellin
authors.affiliation: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stenmark
authors.affiliation: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden martin.gullberg@molbiol.umu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Gullberg
mesh_terms: D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D009474:Neurons / Q000378:metabolism; D058105:Polymerization; D066329:Protein Aggregates / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering; D058112:Septins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D066329:Protein Aggregates; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C502729:SEPTIN12 protein, human; C474315:SEPTIN9 protein, human; D058112:Septins; C407343:septin 3