Alix-mediated assembly of the actomyosin–tight junction polarity complex preserves epithelial polarity and epithelial barrier

Yvan Campos, Xiaohui Qiu, Elida Gomero, Randall Wakefield, Linda Horner, Wojciech Brutkowski, Young-Goo Han, David Solecki, Sharon Frase, Antonella Bongiovanni and Alessandra d’Azzo ()
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Yvan Campos: St Jude Children’s Research Hospital
Xiaohui Qiu: St Jude Children’s Research Hospital
Elida Gomero: St Jude Children’s Research Hospital
Randall Wakefield: Cellular Imaging Shared Resource, St Jude Children’s Research Hospital
Linda Horner: Cellular Imaging Shared Resource, St Jude Children’s Research Hospital
Wojciech Brutkowski: Laboratory of Imaging Tissue Structure and Function, Nencki Institute of Experimental Biology, Polish Academy of Sciences
Young-Goo Han: St Jude Children’s Research Hospital
David Solecki: St Jude Children’s Research Hospital
Sharon Frase: Cellular Imaging Shared Resource, St Jude Children’s Research Hospital
Antonella Bongiovanni: Institute of Biomedicine and Molecular Immunology, National Research Council
Alessandra d’Azzo: St Jude Children’s Research Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier.

Date: 2016
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DOI: 10.1038/ncomms11876

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