INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
Regulation of PKD1-mediated Golgi to cell surface trafficking by Gaq subunit
Autor/es:
CORIA, ANDREA SOLEDAD; MASSERONI, MARÍA LUJÁN; DIAZ AÑEL, A. M.
Revista:
BIOLOGY OF THE CELL
Editorial:
PORTLAND PRESS LTD
Referencias:
Lugar: Londres; Año: 2014 vol. 106 p. 30 - 43
ISSN:
0248-4900
Resumen:
Background information: heterotrimeric GTP-binding proteins play a key role in cell trafficking regulation. Above all, specific Gbetagamma subunits have been shown to be a major component of a signal transduction pathway, which also involves phospholipases C (PLC), protein kinases C (PKC) and D (PKD), whose main function is to regulate transport between Golgi and plasma membrane. It was the involvement of PLC which led us to study the role of the other member of this G protein family, the alpha subunits, in the regulation of membrane fission at the Golgi apparatus. Results: among constitutive active (QL) variants of different G protein alpha subunit sub-families, only GalphaqQL subunits were able to induce Golgi fragmentation, a phenotype that mainly reflects a membrane fission increase at this organelle. This phenotype was not observed with a GalphaqQL palmitoylation mutant, showing the need for a membrane-bounded subunit. Besides, GalphaqQL-dependent Golgi fission was blocked by specific PLC and PKC inhibitors, and in the presence of a PKD1-kinase dead variant. In addition, GalphaqQL was the only alpha subunit capable of inducing PKD1 phosphorylation. Finally, Vesicular Stomatitis Virus thermosensitive mutant glycoprotein (VSVG tsO45) transport assays have demonstrated that GalphaqQL acts directly on Golgi membranes to regulate trafficking between this organelle and plasma membrane. Conclusion: all these results indicate Galphaq subunits for the first time as a regulator of PKD-mediated intracellular trafficking between Golgi apparatus and plasma membrane, opening new perspectives in the understanding of internal trafficking regulation by external signals through G protein coupled receptors.