PUBLICATION
Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis
- Authors
- Walia, V., Cuenca, A., Vetter, M., Insinna, C., Perera, S., Lu, Q., Ritt, D.A., Semler, E., Specht, S., Stauffer, J., Morrison, D.K., Lorentzen, E., Westlake, C.J.
- ID
- ZDB-PUB-200125-13
- Date
- 2019
- Source
- Developmental Cell 50: 229-246.e7 (Journal)
- Registered Authors
- Keywords
- Akt, FIP3, LPA, MC, Rab11 effector switch, Rabin8, WDR44, ciliogenesis, lysophosphatidic acid, mother centriole, phosphorylation, preciliary trafficking
- MeSH Terms
-
- Animals
- Cilia/physiology*
- Gene Expression Regulation*
- Humans
- I-kappa B Kinase/genetics
- I-kappa B Kinase/metabolism*
- Phosphatidylinositol 3-Kinases/genetics
- Phosphatidylinositol 3-Kinases/metabolism*
- Protein Transport
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism*
- Zebrafish
- rab GTP-Binding Proteins/genetics
- rab GTP-Binding Proteins/metabolism*
- PubMed
- 31204173 Full text @ Dev. Cell
Citation
Walia, V., Cuenca, A., Vetter, M., Insinna, C., Perera, S., Lu, Q., Ritt, D.A., Semler, E., Specht, S., Stauffer, J., Morrison, D.K., Lorentzen, E., Westlake, C.J. (2019) Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis. Developmental Cell. 50:229-246.e7.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping