title: A Rab8 guanine nucleotide exchange factor-effector interaction network regulates primary ciliogenesis.
abstract: Primary cilia are microtubule-based solitary membrane projections on the cell surface that play important roles in signaling and development. Recent studies have demonstrated that polarized vesicular trafficking involving the small GTPase Rab8 and its guanine nucleotide exchange factor Rabin8 is essential for primary ciliogenesis. In this study, we show that a highly conserved region of Rabin8 is pivotal for its activation as a guanine nucleotide exchange factor for Rab8. In addition, in its activated conformation, Rabin8 interacts with Sec15, a subunit of the exocyst and downstream effector of Rab8. Expression of constitutively activated Rab8 promotes the association of Sec15 with Rabin8. Using immunofluorescence microscopy, we found that Sec15 co-localized with Rab8 along the primary cilium. Inhibition of Sec15 function in cells led to defects in primary ciliogenesis. The Rabin8-Rab8-Sec15 interaction may couple the activation of Rab8 to the recruitment of the Rab8 effector and is involved in the regulation of vesicular trafficking for primary cilium formation.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Feng
authors.forename: Andreas
authors.initials: A
authors.lastname: Knödler
authors.forename: Jinqi
authors.initials: J
authors.lastname: Ren
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Hong
authors.forename: Shaohui
authors.initials: S
authors.lastname: Huang
authors.forename: Johan
authors.initials: J
authors.lastname: Peränen
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000081410:Germinal Center Kinases; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489222:EXOC6B protein, human; D000081410:Germinal Center Kinases; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins