The University of Southampton
University of Southampton Institutional Repository

Huntingtin is required for epithelial polarity through RAB11A-mediated apical trafficking of PAR3-aPKC

Huntingtin is required for epithelial polarity through RAB11A-mediated apical trafficking of PAR3-aPKC
Huntingtin is required for epithelial polarity through RAB11A-mediated apical trafficking of PAR3-aPKC
The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis.
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
McGuire, John
02e26858-027a-4b14-af92-486c7b743ab2
Yu, Hua
2e06ca55-e893-4976-8fb8-82399d7e02bc
Humbert, Sandrine
c536834f-96fa-4498-b3e0-e44ad54e1de8
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
McGuire, John
02e26858-027a-4b14-af92-486c7b743ab2
Yu, Hua
2e06ca55-e893-4976-8fb8-82399d7e02bc
Humbert, Sandrine
c536834f-96fa-4498-b3e0-e44ad54e1de8

Elias, Salah, McGuire, John, Yu, Hua and Humbert, Sandrine (2015) Huntingtin is required for epithelial polarity through RAB11A-mediated apical trafficking of PAR3-aPKC. PLoS Biology, 13 (5), [e1002142]. (doi:10.1371/journal.pbio.1002142).

Record type: Article

Abstract

The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis.

Text
file - Version of Record
Available under License Creative Commons Attribution.
Download (25MB)

More information

e-pub ahead of print date: 5 May 2015
Published date: 5 May 2015
Organisations: Biomedicine

Identifiers

Local EPrints ID: 408246
URI: http://eprints.soton.ac.uk/id/eprint/408246
PURE UUID: a31e9234-edff-47e5-890c-e0bb0fc0bd68
ORCID for Salah Elias: ORCID iD orcid.org/0000-0003-1005-438X

Catalogue record

Date deposited: 18 May 2017 04:01
Last modified: 16 Mar 2024 04:29

Export record

Altmetrics

Contributors

Author: Salah Elias ORCID iD
Author: John McGuire
Author: Hua Yu
Author: Sandrine Humbert

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×