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J Cell Biol. 2015 Oct 26;211(2):407-34. doi: 10.1083/jcb.201412003.

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

Author information

1
Program in Global Public Health, University of Illinois, Urbana-Champaign, Champaign, IL 61801.
2
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, Champaign, IL 61801 vtang@illinois.edu.

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.

PMID:
26504173
PMCID:
PMC4621826
DOI:
10.1083/jcb.201412003
[Indexed for MEDLINE]
Free PMC Article

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