PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility

The lipid second messenger PI(4,5)P2 modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P2-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promotin...

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Main Authors:	Golub, Tamara, Caroni, Pico
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171909/

id	pubmed-2171909
recordtype	oai_dc
spelling	pubmed-21719092008-03-05 PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility Golub, Tamara Caroni, Pico Research Articles The lipid second messenger PI(4,5)P2 modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P2-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promoting cell surface motility, PI(4,5)P2 directs the assembly of dynamic raft-rich plasmalemmal patches, which promote and sustain protrusive motility. The accumulation of PI(4,5)P2 at rafts, together with Cdc42, promotes patch assembly through N-WASP. The patches exhibit locally regulated PI(4,5)P2 turnover and reduced diffusion-mediated exchange with their environment. Patches capture microtubules (MTs) through patch IQGAP1, to stabilize MTs at the leading edge. Captured MTs in turn deliver PKA to patches to promote patch clustering through further PI(4,5)P2 accumulation in response to cAMP. Patch clustering restricts, spatially confines, and polarizes protrusive motility. Thus, PI(4,5)P2-dependent raft-rich patches enhance local signaling for motility, and their assembly into clusters is regulated through captured MTs and PKA, coupling local regulation of motility to cell polarity, and organization. The Rockefeller University Press 2005-04-11 /pmc/articles/PMC2171909/ /pubmed/15809307 http://dx.doi.org/10.1083/jcb.200407058 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Golub, Tamara Caroni, Pico
spellingShingle	Golub, Tamara Caroni, Pico PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
author_facet	Golub, Tamara Caroni, Pico
author_sort	Golub, Tamara
title	PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
title_short	PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
title_full	PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
title_fullStr	PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
title_full_unstemmed	PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
title_sort	pi(4,5)p2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility
description	The lipid second messenger PI(4,5)P2 modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P2-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promoting cell surface motility, PI(4,5)P2 directs the assembly of dynamic raft-rich plasmalemmal patches, which promote and sustain protrusive motility. The accumulation of PI(4,5)P2 at rafts, together with Cdc42, promotes patch assembly through N-WASP. The patches exhibit locally regulated PI(4,5)P2 turnover and reduced diffusion-mediated exchange with their environment. Patches capture microtubules (MTs) through patch IQGAP1, to stabilize MTs at the leading edge. Captured MTs in turn deliver PKA to patches to promote patch clustering through further PI(4,5)P2 accumulation in response to cAMP. Patch clustering restricts, spatially confines, and polarizes protrusive motility. Thus, PI(4,5)P2-dependent raft-rich patches enhance local signaling for motility, and their assembly into clusters is regulated through captured MTs and PKA, coupling local regulation of motility to cell polarity, and organization.
publisher	The Rockefeller University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171909/
_version_	1611424748683657216

PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility

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