| Literature DB >> 31204173 |
Vijay Walia1, Adrian Cuenca1, Melanie Vetter2, Christine Insinna1, Sumeth Perera1, Quanlong Lu1, Daniel A Ritt1, Elizabeth Semler1, Suzanne Specht1, Jimmy Stauffer1, Deborah K Morrison1, Esben Lorentzen2, Christopher J Westlake3.
Abstract
Serum starvation stimulates cilia growth in cultured cells, yet serum factors associated with ciliogenesis are unknown. Previously, we showed that starvation induces rapid Rab11-dependent vesicular trafficking of Rabin8, a Rab8 guanine-nucleotide exchange factor (GEF), to the mother centriole, leading to Rab8 activation and cilium growth. Here, we demonstrate that through the LPA receptor 1 (LPAR1), serum lysophosphatidic acid (LPA) inhibits Rab11a-Rabin8 interaction and ciliogenesis. LPA/LPAR1 regulates ciliogenesis initiation via downstream PI3K/Akt activation, independent of effects on cell cycle. Akt stabilizes Rab11a binding to its effector, WDR44, and a WDR44-pAkt-phosphomimetic mutant blocks ciliogenesis. WDR44 depletion promotes Rabin8 preciliary trafficking and ciliogenesis-initiating events at the mother centriole. Our work suggests disruption of Akt signaling causes a switch from Rab11-WDR44 to the ciliogenic Rab11-FIP3-Rabin8 complex. Finally, we demonstrate that Akt regulates downstream ciliogenesis processes associated with Rab8-dependent cilia growth. Together, this study uncovers a mechanism whereby serum mitogen signaling regulates Rabin8 preciliary trafficking and ciliogenesis initiation. Published by Elsevier Inc.Entities:
Keywords: Akt; FIP3; LPA; MC; Rab11 effector switch; Rabin8; WDR44; ciliogenesis; lysophosphatidic acid; mother centriole; phosphorylation; preciliary trafficking
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Year: 2019 PMID： 31204173 PMCID： PMC7457226 DOI： 10.1016/j.devcel.2019.05.022
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270