title: 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.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bear
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Tiegang
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Shereen
authors.initials: S
authors.lastname: Abualkhair
authors.forename: Maher A
authors.initials: MA
authors.lastname: Ghamloush
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Ioana
authors.initials: I
authors.lastname: Preston
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Fanburg
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Usamah S
authors.initials: US
authors.lastname: Kayyali
authors.affiliation: Division of Pulmonary, Critical Care and Sleep, Tupper Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Deniz
authors.initials: D
authors.lastname: Toksoz
mesh_terms: D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014746:Vimentin / Q000378:metabolism*; D054358:Withanolides / Q000494:pharmacology; D051178:alpha Catenin / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D014746:Vimentin; D054358:Withanolides; D051178:alpha Catenin; D054460:rho-Associated Kinases; C009684:withaferin A