α5β1 integrin and Cdc 42 participate in axon growth promoted by urokinase plasminogen activator

GONZALO NICOLÁS SPELZINI; JUAN GUILLERMO MAHECHA CASTAÑEDA; VIVIANA SANCHEZ; MARA MEDORI; GABRIEL SCICOLONE; DENIS ALEJANDRO NIETO BERNACHINI; CINDY OLMOS CARREÑO

Mar del Plata

Congreso; XXXII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2017

Sociedad Argentina de Investigación en Neurociencias

Axon growth requires control of mechanisms that include the activation of kinases, and small GTPases and the subsequent reorganization of the actin cytoskeleton. The complex formed by urokinase plasminogen activator (uPA) and its receptor (uPAR) promotes neural migration and neuritogenesis and is closely related to the phosphorylation of the focal adhesion kinase (FAK). The aim of this work was to investigate the role of α5β1 integrin and the small GTPaseCdc42 in uPA:uPAR mediated-axon growth. For this purpose we employed the chicken optic tectum (OT) at 7 days of development (E7). In order to explore whether α5β1 is necessary for uPA:uPAR-mediated axon growth and signaling, we performed explants cultures and evaluated the axon growth with uPA, echistatin (integrin inhibitor) or with both molecules. The level of FAK phosphorylation was evaluated by Western blot in similar experimental conditions. To evaluate whether Cdc42 activity is necessary for uPA:uPAR-mediated axon growth, we compared the axon growth between control and transfected explants with aplasmid coding for an inactive variant of Cdc42, with or without uPA. The results showed that α5β1 integrin is a necessary participant in the intracellular signaling processes activated by uPA:uPAR complex and Cdc42 GTPase is part of the signaling pathways activated after that uPA binds with its receptor and would be responsible for assembly-disassembly of the actin filaments responsible for axonal growth. PIP 00441 CONICET, UBACYT 20020130100526BA