Alpha‐Catulin Co‐Localizes With Vimentin Intermediate Filaments and Functions in Pulmonary Vascular Endothelial Cell Migration via ROCK. Issue 4 (17th September 2015)

• Record Type: Journal Article
• Authors: Bear, Michael D.; Liu, Tiegang; Abualkhair, Shereen; Ghamloush, Maher A.; Hill, Nicholas S.; Preston, Ioana; Fanburg, Barry L.; Kayyali, Usamah S.; Toksoz, Deniz
• Is Part Of: Journal of cellular physiology. Volume 231:Issue 4(2016:Apr.)
• Page Start: 934
• Page End: 943
• Publication Date: 2015-09-17
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25185
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : 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.