A high-volume exoplasmic hemi-TMD is a novel signal for endocytosis and polarity in yeast

AYELEN GONZALEZ MONTORO; GONZALO BIGLIANI; JAVIER VALDEZ TAUBAS

Rosario

Congreso; 50 SAIB; 2014

Sociedad Argentina de Investigación en Buiquímica y Biol. Molecular

A high-volume exoplasmic hemi-TMD is a novel signal for endocytosis and polarity in yeast Ayelén Gonzalez Montoro, Gonzalo Bigliani, and Javier Valdez Taubas. CIQUIBIC, CONICET - Depto de Química Biológica, Fac. Ciencias Quimicas, Univ. Nac. de Córdoba. In Saccharomyces cerevisiae, polarized distribution of membrane proteins is maintained kinetically due to polarized secretion followed by endocytic recycling to the plasma membrane. The classical model for endocytosis of transmembrane proteins involves the recognition of cytosolic signals by adaptor proteins that drive the active concentration of cargoes in endocytic vesicles. As part of a systematic analysis of the influence of Transmembrane Domain (TMD) length and volume in intracellular localization of type-two membrane proteins, we observed that increasing the volume of the residues that constitute the exoplasmic hemi-TMD of the yeast SNARE Sso1, which is distributed homogenously in the plasma membrane, results in its polarized distribution. Expression of this mutant protein in strains affected in either endocytosis or recycling revealed that this polarization is achieved by endocytic cycling. A bioinformatic search of the yeast proteome identified proteins with high-volume exoplasmic hemi-TMDs, some of which exhibit a polarized distribution. We showed that the TMDs of two of these proteins; Hkr1 and Kre6, are also able to confer a polarized distribution to the cytoplasmic domain of Sso1. Overall, our experiments indicate that the geometry of TMDs represent a novel determinant for endocytosis and polarity in vivo.