title: A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution.
abstract: In animal cells, the primary cilium transduces extracellular signals through signaling receptors localized in the ciliary membrane, but how these ciliary membrane proteins are retained in the cilium is unknown. We found that ciliary membrane proteins were highly mobile, but their diffusion was impeded at the base of the cilium by a diffusion barrier. Septin 2 (SEPT2), a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane. SEPT2 depletion resulted in loss of ciliary membrane protein localization and Sonic hedgehog signal transduction, and inhibited ciliogenesis. Thus, SEPT2 is part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Qicong
authors.initials: Q
authors.lastname: Hu
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Milenkovic
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Scott
authors.forename: Maxence V
authors.initials: MV
authors.lastname: Nachury
authors.forename: Elias T
authors.initials: ET
authors.lastname: Spiliotis
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
mesh_terms: D000818:Animals; D054468:Axoneme / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004058:Diffusion; D036681:Fluorescence Recovery After Photobleaching; D019204:GTP-Binding Proteins / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D058112:Septins; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014162:Transfection
chemical_list: D003598:Cytoskeletal Proteins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; C484365:Pkhd1 protein, mouse; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011985:Receptors, Serotonin; D017481:Receptors, Somatostatin; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; C103631:somatostatin receptor 3; D019204:GTP-Binding Proteins; C106863:Sept2 protein, mouse; D058112:Septins