Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan

Autor(es)

Cavalheiro, R. P. ^[1] ; Lima, M. A. ^{[1, 2]} ; Jarrouge-Boucas, T. R. ^[1] ; Viana, G. M. ^[1] ; Lopes, C. C. ^{[3, 1]} ; Coulson-Thomas, V. J. ^{[1, 4]} ; Dreyfuss, J. L. ^{[1, 5]} ; Yates, E. A. ^{[1, 2]} ; Tersariol, I. L. S. ^[1] ; Nader, H. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, SP - Brazil

^[2] Univ Liverpool, Inst Integrat Biol, Dept Biochem, Liverpool, Merseyside - England

^[3] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP - Brazil

^[4] Univ Houston, Coll Optometry, TOSI, Houston, TX - USA

^[5] Univ Fed Sao Paulo, Grp Interdisciplinar Ciencias Exatas Saude, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MATRIX BIOLOGY; v. 63, p. 23-37, NOV 2017.
• Citações Web of Science: 7

Resumo

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in orderto address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/08782-3 - Dinâmica estrutural e funcional do heparam sulfato
• Beneficiário: Marcelo Andrade de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/03964-6 - Glicosaminoglicanos e proteoglicanos: relação estrutura e função
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Temático