Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis.
Akt
FIP3
LPA
MC
Rab11 effector switch
Rabin8
WDR44
ciliogenesis
lysophosphatidic acid
mother centriole
phosphorylation
preciliary trafficking
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
22 07 2019
22 07 2019
Historique:
received:
06
03
2018
revised:
08
02
2019
accepted:
09
05
2019
pubmed:
18
6
2019
medline:
25
1
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31204173
pii: S1534-5807(19)30420-4
doi: 10.1016/j.devcel.2019.05.022
pmc: PMC7457226
mid: NIHMS1618893
pii:
doi:
Substances chimiques
IKBKG protein, human
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
I-kappa B Kinase
EC 2.7.11.10
rab11 protein
EC 3.6.1.-
RAB8A protein, human
EC 3.6.1.-.
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
229-246.e7Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011398
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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