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PI3K class II α controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function.
- Source :
-
Developmental cell [Dev Cell] 2014 Mar 31; Vol. 28 (6), pp. 647-58. - Publication Year :
- 2014
-
Abstract
- Multiple phosphatidylinositol (PtdIns) 3-kinases (PI3Ks) can produce PtdIns3P to control endocytic trafficking, but whether enzyme specialization occurs in defined subcellular locations is unclear. Here, we report that PI3K-C2α is enriched in the pericentriolar recycling endocytic compartment (PRE) at the base of the primary cilium, where it regulates production of a specific pool of PtdIns3P. Loss of PI3K-C2α-derived PtdIns3P leads to mislocalization of PRE markers such as TfR and Rab11, reduces Rab11 activation, and blocks accumulation of Rab8 at the primary cilium. These changes in turn cause defects in primary cilium elongation, Smo ciliary translocation, and Sonic Hedgehog (Shh) signaling and ultimately impair embryonic development. Selective reconstitution of PtdIns3P levels in cells lacking PI3K-C2α rescues Rab11 activation, primary cilium length, and Shh pathway induction. Thus, PI3K-C2α regulates the formation of a PtdIns3P pool at the PRE required for Rab11 and Shh pathway activation.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Female
Fibroblasts cytology
Fibroblasts metabolism
Immunoblotting
Immunoprecipitation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphoinositide-3 Kinase Inhibitors
Protein Transport
RNA, Small Interfering genetics
Receptors, G-Protein-Coupled metabolism
Receptors, Transferrin metabolism
Signal Transduction
Smoothened Receptor
Cell Movement physiology
Cilia physiology
Endosomes metabolism
Phosphatidylinositol 3-Kinases physiology
Phosphatidylinositol Phosphates metabolism
rab GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 28
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 24697898
- Full Text :
- https://doi.org/10.1016/j.devcel.2014.01.022