TRC complex

Abstract: Tail-anchored proteins are a special class of transmembrane proteins, consisting of a cytosolic domain anchored to the phospholipid bilayer by a single hydrophobic segment adjacent to their most C-terminus. Because of their particular topology, the C-terminal anchor must be inserted into membranes post-translationally by mechanisms that differ from the well-known targeting/translocation co-translational pathway. Recently, several advances have created a new understanding of the tail-anchored protein insertion machinery. Because of the essential cellular roles carried out by tail-anchored proteins, including vesicle fusion, regulation of apoptosis and formation of interorganellar contact sites, uncovering the machinery responsible for their biogenesis should further our ability to understand a wide variety of diseases such as forms of cancer caused by activation of the tail-anchored protein oncogene BCL2. Key Concepts Tail-anchored proteins have C-terminal hydrophobic domains. Tail-anchored proteins are inserted post-translationally into the membrane. The GET complex inserts tail-anchored proteins into the endoplasmic reticulum membrane in yeast. The TRC complex chaperones tail-anchored proteins into endoplasmic reticulum membranes in mammals. The mitochondrial outer membrane appears to be the preferred destination of tail-anchored proteins that fail to engage the GET/TRC complex. Functions of the GET/TRC pathway additional to tail-anchored protein targeting are presently under intense investigation. Keywords: tail-anchored proteins; membrane insertion; GET/TRC; ATPase; endoplasmic reticulum; mitochondria