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Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis

  1. Author:
    Walia, Vijay
    Cuenca,Adrian
    Vetter, Melanie
    Insinna, Christine
    Perera, Sumeth
    Lu,Quanlong
    Ritt,Daniel
    Semler, Elizabeth
    Specht,Suzanne
    Stauffer,Jimmy
    Morrison,Deborah
    Lorentzen, Esben
    Westlake,Christopher

  2. Author Address

    Center for Cancer Research, NCI Frederick, Laboratory of Cellular and Developmental Signaling, Frederick, MD 21702, USA., Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10c, 8000 Aarhus C, Denmark., Center for Cancer Research, NCI Frederick, Laboratory of Cellular and Developmental Signaling, Frederick, MD 21702, USA. Electronic address: chris.westlake@nih.gov.,
    1. Year: 2019
    2. Date: JUL 22
    3. Epub Date: 2019 05 31
  2. Journal: Developmental cell
    1. 50
    2. 2
    3. Pages: 229-+
  4. Type of Article: Article
  5. ISSN: 1534-5807
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.devcel.2019.05.022
  3. PMID: 31204173
  4. View record in Web of Science®
  5. WOS: 000476619600011
  6. PII : S1534-5807(19)30420-4

Library Notes

  1. Fiscal Year: FY2018-2019
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