Cell Host & Microbe
Volume 30, Issue 2, 9 February 2022, Pages 216-231.e5
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Article
Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces

https://doi.org/10.1016/j.chom.2021.12.011Get rights and content
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Highlights

  • Apical membranes of mucosal epithelial cells sense virus and enterotoxin binding

  • Virus and toxin sensing causes rapid degradation of the polarity complex components

  • Loss of function in the polarity complex inhibits apical endosome function

  • Depletion of apical endosome blocks further virus and toxin entry

Summary

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.

Keywords

PARD6B
rotavirus
apical endosome
aPKC
trafficking
Cdc42
glycosphingolipids
host defense
enteroids

Data and code availability

Mass spectrometry data is available as a data table (Table 1). This paper does not report original code. Additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

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These authors contributed equally

8

Present address: Departments of Pathology and Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

9

Present address: Department of Endoscopy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

10

Present address: Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA

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Lead contact