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 m...

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Bibliographic Details
Published in:PLoS biology 2015-05, Vol.13 (5), p.e1002142-e1002142
Main Authors: Elias, Salah, McGuire, John Russel, Yu, Hua, Humbert, Sandrine
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion Molecules - metabolism
Cell division
Cellular Biology
Defects
Development and progression
Dogs
Epithelial cells
Epithelium - embryology
Female
Gene mutations
Genetic aspects
Health aspects
Humans
Huntingtin Protein
Huntington's chorea
Identification and classification
Kinases
Life Sciences
Madin Darby Canine Kidney Cells
Mammary Glands, Animal - embryology
Metastasis
Mice
Morphogenesis
Nerve Tissue Proteins - metabolism
Nuclear Proteins - metabolism
Pregnancy
Protein Kinase C - metabolism
Proteins
rab GTP-Binding Proteins - metabolism
Rodents
Transport Vesicles - physiology
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Summary: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.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.1002142