A ribosome‐associating chaperone that facilitates membrane protein targeting

Insertion of proteins into biological membranes is a fundamental process vital to all organisms. The hydrophobic transmembrane segments of membrane proteins must be recognized, shielded constantly during their targeting to the correct intracellular membrane, and guided into the lipid bilayer. These events must be highly regulated to prevent inappropriate exposure of transmembrane domains to the aqueous cytosol. We recently discovered a new, widely conserved membrane protein insertion pathway for ‘tail‐anchored’ membrane proteins. These membrane proteins play wide roles in numerous areas of cell biology, and understanding their faithful insertion represents a paradigm for how hydrophobic proteins are trafficked through the cytosol. Remarkably, this pathway includes a ribosome‐associating chaperone that initially captures tail‐anchored membrane proteins and delivers them to a dedicated targeting factor. Further analysis is revealing new roles for this chaperone in not only protein targeting, but also quality control of membrane proteins. Our functional studies of this new chaperone complex and its role in handling membrane proteins will be discussed.