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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...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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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. |
format | Text |
id | pubmed-3082196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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