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A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells

The membrane of the primary cilium is continuous with the plasma membrane but compositionally distinct. Although some membrane proteins concentrate in the cilium, others such as podocalyxin/gp135 are excluded. We found that exclusion reflects a saturable selective retention mechanism. Podocalyxin is...

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Detalles Bibliográficos
Autores principales: Francis, Stephen S., Sfakianos, Jeff, Lo, Bryan, Mellman, Ira
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082196/
https://www.ncbi.nlm.nih.gov/pubmed/21444686
http://dx.doi.org/10.1083/jcb.201009001
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author Francis, Stephen S.
Sfakianos, Jeff
Lo, Bryan
Mellman, Ira
author_facet Francis, Stephen S.
Sfakianos, Jeff
Lo, Bryan
Mellman, Ira
author_sort Francis, Stephen S.
collection PubMed
description The membrane of the primary cilium is continuous with the plasma membrane but compositionally distinct. Although some membrane proteins concentrate in the cilium, others such as podocalyxin/gp135 are excluded. We found that exclusion reflects a saturable selective retention mechanism. Podocalyxin is immobilized by its PDZ interaction motif binding to NHERF1 and thereby to the apical actin network via ERM family members. The retention signal was dominant, autonomous, and transferable to membrane proteins not normally excluded from the cilium. The NHERF1-binding domains of cystic fibrosis transmembrane conductance regulator and Csk-binding protein were also found to act as transferable retention signals. Addition of a retention signal could inhibit the ciliary localization of proteins (e.g., Smoothened) containing signals that normally facilitate concentration in the ciliary membrane. Proteins without a retention signal (e.g., green fluorescent protein–glycosylphosphatidylinositol) were found in the cilium, suggesting entry was not impeded by a diffusion barrier or lipid microdomain. Thus, a hierarchy of interactions controls the composition of the ciliary membrane, including selective retention, selective inclusion, and passive diffusion.
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spelling pubmed-30821962011-10-04 A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells Francis, Stephen S. Sfakianos, Jeff Lo, Bryan Mellman, Ira J Cell Biol Research Articles The membrane of the primary cilium is continuous with the plasma membrane but compositionally distinct. Although some membrane proteins concentrate in the cilium, others such as podocalyxin/gp135 are excluded. We found that exclusion reflects a saturable selective retention mechanism. Podocalyxin is immobilized by its PDZ interaction motif binding to NHERF1 and thereby to the apical actin network via ERM family members. The retention signal was dominant, autonomous, and transferable to membrane proteins not normally excluded from the cilium. The NHERF1-binding domains of cystic fibrosis transmembrane conductance regulator and Csk-binding protein were also found to act as transferable retention signals. Addition of a retention signal could inhibit the ciliary localization of proteins (e.g., Smoothened) containing signals that normally facilitate concentration in the ciliary membrane. Proteins without a retention signal (e.g., green fluorescent protein–glycosylphosphatidylinositol) were found in the cilium, suggesting entry was not impeded by a diffusion barrier or lipid microdomain. Thus, a hierarchy of interactions controls the composition of the ciliary membrane, including selective retention, selective inclusion, and passive diffusion. The Rockefeller University Press 2011-04-04 /pmc/articles/PMC3082196/ /pubmed/21444686 http://dx.doi.org/10.1083/jcb.201009001 Text en © 2011 Francis et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Francis, Stephen S.
Sfakianos, Jeff
Lo, Bryan
Mellman, Ira
A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title_full A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title_fullStr A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title_full_unstemmed A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title_short A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
title_sort hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082196/
https://www.ncbi.nlm.nih.gov/pubmed/21444686
http://dx.doi.org/10.1083/jcb.201009001
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