Publication Date
2-9-2022
Journal
Cell Host & Microbe
DOI
10.1016/j.chom.2021.12.011
PMID
35143768
PMCID
PMC8852832
PubMedCentral® Posted Date
2-9-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Bacterial Toxins, Cell Polarity, Endosomes, Epithelial Cells, Protein Kinase C, Viruses
Abstract
Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or virus-binding initiates degradation of PARD6B. The loss of PARD6B causes the depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface, thus enabling a form of cell-autonomous host defense.