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

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.

USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells

“…In recent years, regulatory factors of vimentin have been identified. For example, alpha-catulin colocalizes with vimentin intermediate filaments and functions in pulmonary vascular endothelial cell migration via ROCK [ 39 ], and proteomic analysis revealed the important role of vimentin in human HeLa cells [ 40 ]. Here, we found that vimentin was upregulated in human GC tissues and cell lines, and the upregulation of vimentin promoted the aggressiveness of GC cells.…”

Intermediate Filaments at the Junction of Mechanotransduction, Migration, and Development

“…It is well-known that intermediate filament architecture is reorganized in response to cell migration stimuli. α-Catulin, a scaffold for the ROCK signalosome (Park et al, 2002 ), co-localizes with vimentin intermediate filaments and contributes to vascular endothelial cell migration (Bear et al, 2016 ). In addition, vimentin filaments are also essential for VASP localization and phosphorylation by cGMP dependent kinase in endothelial cells (Lund et al, 2010 ).…”

Regulation of Hematopoiesis and Osteogenesis by Blood Vessel–Derived Signals

“…However, α-catulin is expressed by heterogeneous populations of HSPCs, including stromal cells and ECs (Chen et al 2016). Expression of α-catulin indicates EC activation and migratory state (Bear et al 2016). Similarly, such expression may also allow for the identification of metabolically activated HSPCs in BM perisinusoidal niches.…”