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PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function
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)...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042153/ https://www.ncbi.nlm.nih.gov/pubmed/24697898 http://dx.doi.org/10.1016/j.devcel.2014.01.022 |
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author | Franco, Irene Gulluni, Federico Campa, Carlo C. Costa, Carlotta Margaria, Jean Piero Ciraolo, Elisa Martini, Miriam Monteyne, Daniel De Luca, Elisa Germena, Giulia Posor, York Maffucci, Tania Marengo, Stefano Haucke, Volker Falasca, Marco Perez-Morga, David Boletta, Alessandra Merlo, Giorgio R. Hirsch, Emilio |
author_facet | Franco, Irene Gulluni, Federico Campa, Carlo C. Costa, Carlotta Margaria, Jean Piero Ciraolo, Elisa Martini, Miriam Monteyne, Daniel De Luca, Elisa Germena, Giulia Posor, York Maffucci, Tania Marengo, Stefano Haucke, Volker Falasca, Marco Perez-Morga, David Boletta, Alessandra Merlo, Giorgio R. Hirsch, Emilio |
author_sort | Franco, Irene |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4042153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40421532014-06-04 PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function Franco, Irene Gulluni, Federico Campa, Carlo C. Costa, Carlotta Margaria, Jean Piero Ciraolo, Elisa Martini, Miriam Monteyne, Daniel De Luca, Elisa Germena, Giulia Posor, York Maffucci, Tania Marengo, Stefano Haucke, Volker Falasca, Marco Perez-Morga, David Boletta, Alessandra Merlo, Giorgio R. Hirsch, Emilio Dev Cell Article 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. Cell Press 2014-03-31 /pmc/articles/PMC4042153/ /pubmed/24697898 http://dx.doi.org/10.1016/j.devcel.2014.01.022 Text en © 2014 Elsevier Inc. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Franco, Irene Gulluni, Federico Campa, Carlo C. Costa, Carlotta Margaria, Jean Piero Ciraolo, Elisa Martini, Miriam Monteyne, Daniel De Luca, Elisa Germena, Giulia Posor, York Maffucci, Tania Marengo, Stefano Haucke, Volker Falasca, Marco Perez-Morga, David Boletta, Alessandra Merlo, Giorgio R. Hirsch, Emilio PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title | PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title_full | PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title_fullStr | PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title_full_unstemmed | PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title_short | PI3K Class II α Controls Spatially Restricted Endosomal PtdIns3P and Rab11 Activation to Promote Primary Cilium Function |
title_sort | pi3k class ii α controls spatially restricted endosomal ptdins3p and rab11 activation to promote primary cilium function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042153/ https://www.ncbi.nlm.nih.gov/pubmed/24697898 http://dx.doi.org/10.1016/j.devcel.2014.01.022 |
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