CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area

Research output: Contribution to journalArticle

Abstract

Maintaining the correct ratio of apical, basal, and lateral membrane domains is important for epithelial physiology. Here, we show that CD2AP is a critical determinant of epithelial membrane proportions. Depletion of CD2AP or phosphoinositide 3-kinase (PI3K) inhibition results in loss of F-actin and expansion of apical-basal domains, which comes at the expense of lateral membrane height in MDCK cells. We demonstrate that the SH3 domains of CD2AP bind to PI3K and are necessary for PI3K activity along lateral membranes and constraining cell area. Tethering the SH3 domains of CD2AP or p110γ to the membrane is sufficient to rescue CD2AP-knockdown phenotypes. CD2AP and PI3K are both upstream and downstream of actin polymerization. Since CD2AP binds to both actin filaments and PI3K, CD2AP might bridge actin assembly to PI3K activation to form a positive feedback loop to support lateral membrane extension. Our results provide insight into the squamous to cuboidal to columnar epithelial transitions seen in complex epithelial tissues in vivo.

Original languageEnglish (US)
JournalThe Journal of cell biology
Volume219
Issue number1
DOIs
StatePublished - Jan 6 2020

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1-Phosphatidylinositol 4-Kinase
Phosphatidylinositol 3-Kinases
Actins
Epithelial Cells
Membranes
src Homology Domains
Madin Darby Canine Kidney Cells
Actin Cytoskeleton
Polymerization
Epithelium
Cell Membrane
Phenotype

ASJC Scopus subject areas

  • Cell Biology

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CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area. / Wang, Yuou; Brieher, William M.

In: The Journal of cell biology, Vol. 219, No. 1, 06.01.2020.

Research output: Contribution to journalArticle

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