Scientific Reports

Scientific Report 2006-2007 for the Laboratory of Olivier Vincent -

Functional analysis of genes involved in cell signaling and conserved from yeast to humans in the model organism S. cerevisiae

Group Leader
Vincent -, Olivier
Graduate Students
Herranz Fernández, Silvia
Herrador Fernández, Antonio (from Oct 2006 )
Navas, Maria Angeles (Universidad Complutense de Madrid)
Orozco, Esther (CINVESTAV, México)
Undergraduate Students
Lara Astiaso, David (from May 2007 )
García Urbina, María del Prado (from Jul 2007 to Jul 2007 )

Research topics

Functional analysis of saccharomyces cerevisiae homologues of mammalian arrestins

( Herrador, A. , Herranz, S. , Lara, D. , Vincent, O. )

Arrestins plays a key role in the regulation of the seven-transmembrane receptors in mammals. These receptors, on the other hand, are involved in a large number of physiological processes and are the target of 40% of the therapeutic drugs currently used. Arrestins have been identified in metazoans but no arrestin homologues had been reported in fungi or plants. Our previous results have shown that palF/Rim8, a component of the Pal/Rim pH signalling pathway in fungi, is homologous to arrestins. PalF/Rim8 strongly interacts with the 7TM protein PalH/Rim21, a putative pH sensor in this signalling pathway. In addition, our previous studies suggest that the same regulatory mechanisms (phosphorylation and ubiquitination) are involved in the regulation of mammal arrestins and their fungal homologues. The main goal of our work is using these proteins as a model to study the molecular mechanisms involved in the regulation of mammalian arrestins. We started the characterization of the molecular mechanisms involved in the regulation of Rim8 in the yeast Saccharomyces cerevisiae. First, we used reporters to study the regulation of the Rim signalling pathway by ambient pH and the role of the Rim proteins in this process. Second, we showed that Rim8, as mammal arrestin, is ubiquitinated and phosphorylated.

García-Herrero, CM. , Galán, M. , Vincent, O. , Flández, B. , Gargallo, M. , Delgado-Alvarez, E. , Blázquez, E. , Navas, MA. (2007). Functional analysis of human glucokinase gene mutations causing MODY2: exploring the regulatory mechanisms of glucokinase activity. Diabetologia. 50: 325-333.

Galindo, A. , Hervás-Aguilar, A. , Rodríguez-Galán, O. , Vincent, O. , Arst, HN.Jr , Tilburn, J. , Peñalva, MA. (2007). PalC, one of two Bro1 domain proteins in the fungal pH signalling pathway, localizes to cortical structures and binds Vps32. Traffic. 8: 1346-1364.

Galán, M. , Vincent, O. , Roncero, I. , Azriel, S. , Boix-Pallares, P. , Delgado-Alvarez, E. , Díaz-Cadórniga, F. , Blázquez, E. , Navas, MA. (2006). Effects of novel maturity-onset diabetes of the young (MODY)-associated mutations on glucokinase activity and protein stability. Biochem J. 393: 389-396.

Navas, MA. , Galan, M. , Vincent, O. , Roncero, I. , Azriel, S. , Boix-Pallares, P. , Delgado-Alvarez, E. , Diaz-Cadórniga, F. , Blázquez, E. (2006). Gene symbol: GCK. Disease: diabetes, MODY. Hum Genet. 119: 2006-2006.

Financial Support

“Analisis funcional de proteínas de Saccharomyces cerevisiae homólogas de las arrestinas de mamíferos.” Financiado por: Dirección general de Investigación MEC. Year 2006-2008

“Caracterización de proteínas relacionadas con las arrestinas en Saccharomyces cerevisiae.” Financiado por: CSIC-I3. Year 2006-2007