Transmembrane-domain shape is a novel endocytosis signal for single-spanning membrane proteins

GONZALO BIGLIANI; AYELEN GONZALEZ MONTORO; JAVIER VALDEZ TAUBAS

CABA

Congreso; Reunión conjunta de sociedades de Biociencias,; 2017

SAIB

TRANSMEMBRANE-DOMAIN SHAPE IS A NOVEL ENDOCYTOSIS SIGNAL FOR SINGLE-SPANNING MEMBRANE PROTEINSEndocytosis is crucial for all cells as it allows them to incorporate material from the extracellular space and control the availability of transmembrane proteins in the plasma membrane. The classical model for endocytosis of membrane proteins involves cytosolic signals that interact with adaptor proteins, driving active concentration of cargo in endocytic vesicles. In yeast, endocytosis followed by recycling to the plasma membrane results in a polarised distribution of membrane proteins by a kinetic mechanism. Here we report that increasing the volume of the residues that constitute the exoplasmic half of the transmembrane domain in the yeast SNARE Sso1, results in its polarised distribution at the plasma membrane. Expression of this chimera in strains affected in either endocytosis or recycling revealed that this polarisation is achieved by endocytic cycling. A bioinformatics search of the Saccharomyces cerevisiae proteome identified several proteins with high-volume exoplasmic hemi-TMDs. Our experiments indicate that TMDs of these proteins can confer a polarised distribution to the Sso1 cytoplasmic domain, indicating that the shape of the TMD can act as a novel endocytosis and polarity signal in yeast. Additionally, high-volume exoplasmic hemi-TMDs can act as an endocytosis signal in mammalian cells in culture.