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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). (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.

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Published date: 5 May 2015
Organisations: Biomedicine

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Local EPrints ID: 408246
URI: https://eprints.soton.ac.uk/id/eprint/408246
PURE UUID: a31e9234-edff-47e5-890c-e0bb0fc0bd68

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Date deposited: 18 May 2017 04:01
Last modified: 23 Sep 2019 17:40

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