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Time-lapse analysis confirmed that Gas3\/PMP22 can modulate cell spreading, and this effect was strengthened after inhibition of phosphoinositide 3-kinase. Using the active form of the small GTPase RhoA, we have been able to dissect the different Gas3\/PMP22 biological activities. RhoA counteracted the Gas3\/PMP22-dependent morphological response but was unable to neutralize the apoptotic response. Treatment of NIH3T3 cells with cytotoxic necrotizing factor 1, which activates endogenous Rho, also counteracted Gas3\/PMP22-mediated cell shape and spreading changes. Treatment of REF 52 cells, which are unresponsive to Gas3\/PMP22 overexpression, with the C3 exoenzyme, inhibiting Rho activity, renders REF 52 cells responsive to Gas3\/PMP22 overexpression for cell shape and spreading changes. Finally, assembly of stress fibers and focal adhesions complexes, in response to lysophosphatidic acid\u2013induced endogenous Rho activation, was impaired in Gas3\/PMP22-overexpressing cells. We hypothesize that cell shape and spreading regulated by Gas3\/PMP22 through the Rho GTPase might have an important role during Schwann cells differentiation and myelinization.<\/jats:p>","DOI":"10.1091\/mbc.10.7.2441","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T23:34:04Z","timestamp":1372808044000},"page":"2441-2459","source":"Crossref","is-referenced-by-count":65,"title":["Rho-dependent Regulation of Cell Spreading by the Tetraspan Membrane Protein Gas3\/PMP22"],"prefix":"10.1091","volume":"10","author":[{"given":"Claudio","family":"Brancolini","sequence":"first","affiliation":[{"name":"Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, 34142 Trieste, Italy;"},{"name":"Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia-Universit\u00e1 di Udine, 33100 Udine, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Marzinotto","sequence":"additional","affiliation":[{"name":"Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, 34142 Trieste, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Edomi","sequence":"additional","affiliation":[{"name":"Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, 34142 Trieste, Italy;"},{"name":"Dipartimento di Biologia Universit\u00e1 di Trieste, 34100 Trieste, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Agostoni","sequence":"additional","affiliation":[{"name":"Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, 34142 Trieste, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Dipartimento di Ultrastruttura, Istituto Superiore di Sanit\u00e1, 00161 Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Werner","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Schneider","sequence":"additional","affiliation":[{"name":"Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, 34142 Trieste, Italy;"},{"name":"Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia-Universit\u00e1 di Udine, 33100 Udine, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/ng1195-274","volume":"11","author":"Adlkofer K.","year":"1995","journal-title":"Nat. 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