Fatty acylation of proteins: influence on membrane association and intracellular trafficking

DANIOTTI J.L.

La Serena

Workshop; 2016 EMBO Workshop: Actualizations in membrane trafficking in health and disease; 2016

EMBO and local organizing committee

A wide variety of proteins are modified by covalently-linked fatty acids and/or prenyl groups, which may confer reversible association of these lipid-modified proteins with membranes. Moreover, each distinct fatty acid or prenyl moiety provides particular information to assist proteins in finding their correct spatial organization and proper biological function.We have focused on understanding the consequences of proteins S-acylation on intracellular trafficking using as model protein members of the Ras family GTPases. S-acylation, unlike other lipid modification such as N-myristoylation and prenylation, is the only reversible fatty-acid modification. Despite the progress that has been made in identifying and characterizing protein acyltransferases involved in S-acylation, much less is known about the thioesterases participating in protein deacylation. The identification in our laboratory of the second bona fide protein thioesterase (APT2), allow us to better characterize the deacylation process and its role in the spatial distribution of peripheral proteins. Overall, our findings illustrate how lipid modification of proteins plays an important role in dictating precise intracellular movements within the cells by regulating membrane-cytosol exchange and/or by modifying the flux of the proteins through vesicular transport systems.