2. Academic Validation
  3. Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis

Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis

  • Dev Cell. 2019 Jul 22;50(2):229-246.e7. doi: 10.1016/j.devcel.2019.05.022.
Vijay Walia 1,  Adrian Cuenca 1,  Melanie Vetter 2,  Christine Insinna 1,  Sumeth Perera 1,  Quanlong Lu 1,  Daniel A Ritt 1,  Elizabeth Semler 1,  Suzanne Specht 1,  Jimmy Stauffer 1,  Deborah K Morrison 1,  Esben Lorentzen 2,  Christopher J Westlake 3
Affiliations

Affiliations

  • 1 Center for Cancer Research, NCI Frederick, Laboratory of Cellular and Developmental Signaling, Frederick, MD 21702, USA.
  • 2 Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10c, 8000 Aarhus C, Denmark.
  • 3 Center for Cancer Research, NCI Frederick, Laboratory of Cellular and Developmental Signaling, Frederick, MD 21702, USA. Electronic address: chris.westlake@nih.gov.
PMID: 31204173 DOI: 10.1016/j.devcel.2019.05.022
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.

Keywords

Akt; FIP3; LPA; MC; Rab11 effector switch; Rabin8; WDR44; ciliogenesis; lysophosphatidic acid; mother centriole; phosphorylation; preciliary trafficking.

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