Membrane protein trafficking in mammalian cells
With the exception of proteins that are synthesized in the cytosol and posttranslationally become inserted into membranes of e.g. mitochondria or peroxisomes, membrane proteins are transported to their site of function or cleared from there by membrane traffic via small vesicles or larger transport intermediates. The incorporation of membrane proteins into a forming vesicle is mediated by adaptor proteins which bind to so-called sorting signals located in the cytoplasmic tails of the proteins (1, 2). Today more than a dozen of adaptors are known, some of which are monomeric, while others function as oligomers. The heterotetrameric adaptor complexes (AP complexes) belong to the latter group and are key factors for membrane protein sorting during endocytosis from the plasma membrane, in endosomes and in the TGN. 4 AP complexes are known (AP1, AP2, AP3 and AP4) which are all composed of 2 large subunits of 90-130 kDa, a medium subunit of app. 50 kDa and a small subunit of 20 kDa. AP complexes not only bind cargo membrane sorting signals but they also recruit other factors required for vesicle formation (3, 4). The general concept of AP complex function is well established, however how their function is regulated is only poorly understood and thus one issue we address in our lab. Another issue we currently focus on is the identification of the composition (membrane lipids and proteins and included cargo) of a transport vesicle, which is of great importance in order to understand the underlying mechanisms of vesicle formation. Last but not least, loss of AP complex function as well as mutated sorting signals can lead to missorting of membrane proteins and thus eventually to disease that are named accordingly trafficking-related diseases (5, 6). Part of our work addresses the molecular basis of such diseases.
27 Juli 2015
Institut für Biochemie I, Joseph-Stelzmann-Strasse 52, D50931 Köln
Anregungen und Wünsche: Gudrun Konertz