S-acylation of Ganglioside Glycosyltransferases

SABRINA CHUMPEN RAMIREZ; JAVIER VALDEZ TAUBAS

Rosario

Congreso; L Reunión Anual SAIB 2014; 2014

S-acylation is a post translational modification consisting in the addition of lipid molecules to cysteine residues of the proteins trough a thioesther bond. It is the only lipid modification that is reversible and susceptible to be regulated. Soluble proteins that are S-acylated can reach a stable binding to membranes but the function of this modification on transmembrane proteins is not clear. In yeast it was shown that S-acylation of the type II transmembrane SNARE TlgI it is involved in its stability but the role in mammalian SNAREs and other type II transmembrane proteins, like glycosyltransferases was not described. Glycosyltransferases are Golgi resident proteins involved in protein and lipid glycosylation. Mutations in these proteins are related to some disorders and human diseases so their functional consequences have been extensible studied. To date not lipid modifications have been reported for them. The aim of this work is to study type II transmembrane proteins S-acylation, the functional consequences of this modification and the acyltransferase involved in this reaction, using mammalian cells as a model and plasmid constructions expressing the Ntds of gangliosides glycosyltransferases as well the full length versions.We have found that gangliosides glycosyltransferases are palmitoylated in CHO-K1 cells and this modification could be involved in homodimerization of these proteins. Overexpression experiments suggest that DHHC4 could be the palmitoyltransferase involved in ganglioside glycosyltransferases modification in the endoplasmic reticulum.