Geometric features of trasnmebrane domains are major determinants of Golgi Localization

RODRIGO QUIROGA; ALEJANDRA TRENCHI; AYELEN GONZALEZ MONTORO; JAVIER VALDEZ TAUBAS; HUGO MACCIONI

Mendoza

Congreso; XLVIII SAIB; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Subcellular localization of bitopic transmembrane (TM) proteins is achieved through a variety of mechanisms, of which the most studied is direct or indirect interaction with coatomers using citoplasmic small linear motifs (SLIMs). However, vesicular transport from the Golgi to the plasma membrane is mostly carried out in vesicles that apparently form without the need of a coatomer. Additionally, no SLIMs have been described to determine Golgi export, and only one SLIM has been proposed to participate in Golgi retention, though our bioinformatic queries have estimated that it is only present in 12% of Golgi resident proteins. We have constructed a dataset of proteins with known subcellular locations and studied their TM domains. Geometric properties of TM domains seem to determine Golgi retention or Golgi export, independently of any SLIMs present in cytoplasmic tails of integral membrane proteins. Additionally, using the Saccharomyces cerevisiae SNAREs Sft1 (Golgi apparatus) and Sso1 (plasma membrane) as model proteins, we modified the length and amino acid composition of their TMDs and determined their subcellular localization both in yeast and in mammalian cells. We find that short TMDs with voluminous exoplasmic hemi-TMDs confer golgi residence while longer TMDs with less voluminous exoplasmic hemi-TMDs confer plasma membrane residence to these proteins.