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A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions

The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI)...

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Autores principales: Fan, Shuling, Fogg, Vanessa, Wang, Qian, Chen, Xiao-Wei, Liu, Chia-Jen, Margolis, Ben
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064851/
https://www.ncbi.nlm.nih.gov/pubmed/17646395
http://dx.doi.org/10.1083/jcb.200609096
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author Fan, Shuling
Fogg, Vanessa
Wang, Qian
Chen, Xiao-Wei
Liu, Chia-Jen
Margolis, Ben
author_facet Fan, Shuling
Fogg, Vanessa
Wang, Qian
Chen, Xiao-Wei
Liu, Chia-Jen
Margolis, Ben
author_sort Fan, Shuling
collection PubMed
description The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI). We report that CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles. Knockdown of CRB3-CLPI leads to both a loss of cilia and a multinuclear phenotype associated with centrosomal and spindle abnormalities. Using protein purification, we find that CRB3-CLPI interacts with importin β-1 in a Ran-regulated fashion. Importin β-1 colocalizes with CRB3-CLPI during mitosis, and a dominant-negative form of importin β-1 closely phenocopies CRB3-CLPI knockdown. Knockdown of importin β-1 blocks targeting of CRB3-CLPI to the spindle poles. Our data suggest an expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins.
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spelling pubmed-20648512008-01-30 A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions Fan, Shuling Fogg, Vanessa Wang, Qian Chen, Xiao-Wei Liu, Chia-Jen Margolis, Ben J Cell Biol Research Articles The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI). We report that CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles. Knockdown of CRB3-CLPI leads to both a loss of cilia and a multinuclear phenotype associated with centrosomal and spindle abnormalities. Using protein purification, we find that CRB3-CLPI interacts with importin β-1 in a Ran-regulated fashion. Importin β-1 colocalizes with CRB3-CLPI during mitosis, and a dominant-negative form of importin β-1 closely phenocopies CRB3-CLPI knockdown. Knockdown of importin β-1 blocks targeting of CRB3-CLPI to the spindle poles. Our data suggest an expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins. The Rockefeller University Press 2007-07-30 /pmc/articles/PMC2064851/ /pubmed/17646395 http://dx.doi.org/10.1083/jcb.200609096 Text en Copyright © 2007, 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/).
spellingShingle Research Articles
Fan, Shuling
Fogg, Vanessa
Wang, Qian
Chen, Xiao-Wei
Liu, Chia-Jen
Margolis, Ben
A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title_full A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title_fullStr A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title_full_unstemmed A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title_short A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
title_sort novel crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064851/
https://www.ncbi.nlm.nih.gov/pubmed/17646395
http://dx.doi.org/10.1083/jcb.200609096
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