Alpha-Catulin Co-Localizes With Vimentin Intermediate Filaments and Functions in Pulmonary Vascular Endothelial Cell Migration via ROCK

J Cell Physiol. 2016 Apr;231(4):934-43. doi: 10.1002/jcp.25185. Epub 2015 Sep 17.


The ubiquitous α-catulin acts as a scaffold for distinct signalosomes including RhoA/ROCK; however, its function is not well understood. While α-catulin has homology to the cytoskeletal linkers α-catenin and vinculin, it appears to be functionally divergent. Here we further investigated α-catulin function in pulmonary vascular endothelial cells (VEC) on the premise that α-catulin has a unique cytoskeletal role. Examination of endogenous α-catulin intracellular localization by immunofluorescence revealed a highly organized cytosolic filamentous network suggestive of a cytoskeletal system in a variety of cultured VEC. Double-immunofluorescence analyses of VEC showed endogenous α-catulin co-localization with vimentin intermediate filaments. Similar to vimentin, α-catulin was found to distribute into detergent-soluble and -insoluble fractions. Treatment of VEC with withaferinA, an agent that targets vimentin filaments, disrupted the α-catulin network distribution and altered α-catulin solubility. Vimentin participates in cell migration, and withaferinA was found to inhibit VEC migration in vitro; similarly, α-catulin knock-down reduced VEC migration. Based on previous reports showing that ROCK modulates vimentin, we found that ROCK depletion attenuated VEC migration; furthermore, α-catulin depletion was shown to reduce ROCK-induced signaling. These findings indicate that α-catulin has a unique function in co-localization with vimentin filaments that contributes to VEC migration via a pathway that may involve ROCK signaling. J. Cell. Physiol. 231: 934-943, 2016. © 2015 Wiley Periodicals, Inc.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cattle
  • Cell Movement* / drug effects
  • Cytosol / metabolism
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Intermediate Filaments / drug effects
  • Intermediate Filaments / metabolism*
  • Lung / cytology*
  • Protein Transport / drug effects
  • Rats
  • Signal Transduction / drug effects
  • Solubility
  • Vimentin / metabolism*
  • Withanolides / pharmacology
  • alpha Catenin / metabolism*
  • rho-Associated Kinases / metabolism*


  • Vimentin
  • Withanolides
  • alpha Catenin
  • rho-Associated Kinases
  • withaferin A