Synaptopodin couples epithelial contractility to α-actinin-4-dependent junction maturation

Nivetha Kannan, Vivian W. Tang

Research output: Contribution to journalArticle

Abstract

The epithelial junction experiences mechanical force exerted by endogenous actomyosin activities and from interactions with neighboring cells. We hypothesize that tension generated at cell-cell adhesive contacts contributes to the maturation and assembly of the junctional complex. To test our hypothesis, we used a hydraulic apparatus that can apply mechanical force to intercellular junction in a confluent monolayer of cells. We found that mechanical force induces α-actinin-4 and actin accumulation at the cell junction in a time- and tension-dependent manner during junction development. Intercellular tension also induces α-actinin-4-dependent recruitment of vinculin to the cell junction. In addition, we have identified a tension-sensitive upstream regulator of α-actinin-4 as synaptopodin. Synaptopodin forms a complex containing α-actinin-4 and β-catenin and interacts with myosin II, indicating that it can physically link adhesion molecules to the cellular contractile apparatus. Synaptopodin depletion prevents junctional accumulation of α-actinin-4, vinculin, and actin. Knockdown of synaptopodin and α-actinin-4 decreases the strength of cell-cell adhesion, reduces the monolayer permeability barrier, and compromises cellular contractility. Our findings underscore the complexity of junction development and implicate a control process via tension-induced sequential incorporation of junctional components.

Original languageEnglish (US)
Pages (from-to)407-434
Number of pages28
JournalJournal of Cell Biology
Volume211
Issue number2
DOIs
StatePublished - Oct 26 2015

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Actinin
Intercellular Junctions
Vinculin
Actins
Myosin Type II
Catenins
Actomyosin
Cell Adhesion
Adhesives
Permeability

ASJC Scopus subject areas

  • Cell Biology

Cite this

Synaptopodin couples epithelial contractility to α-actinin-4-dependent junction maturation. / Kannan, Nivetha; Tang, Vivian W.

In: Journal of Cell Biology, Vol. 211, No. 2, 26.10.2015, p. 407-434.

Research output: Contribution to journalArticle

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