short length transmembrane domains having voluminous exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex

RODRIGO QUIROGA; ALEJANDRA TRENCHI; AYELÉN GONZALEZ MONTORO; JAVIER VALDEZ TAUBAS; HUGO J.F MACCIONI

Bari

Congreso; 54 international conference on the bioscience of lipids; 2013

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.