Molecular Dissection of Clathrin Coat Formation and Receptor Sorting

Abstract

Traffic between intracellular compartments requires a special mechanism to transport proteins, lipids and cargo molecules from a donor to an acceptor organelle. This process is mediated by vesicles that bud off the donor membrane and fuse with an acceptor membrane. This solves the problem of selection, because the cargo molecules are concentrated into the vesicles before the vesicle separates from the donor membrane. The first step in cargo concentration is the binding of cargo molecules to the lumenal domain of a transmembrane receptor. This is followed by the interaction of the cytoplasmic domain of the receptor with a protein complex that is believed to trigger the formation of a protein coat, in turn leading to the formation of a pit in the membrane that will eventually become a vesicle. This coupling of cargo concentration and coat formation ensures efficient cargo loading into the assembling vesicles. The neck of the vesicle then narrows, and the vesicle finally pinches off the membrane. At this point the protein coat is removed, and the vesicle is targeted to the acceptor compartment, eventually fusing with the target membrane. Among the best understood processes for moving receptors and ligands are clathrin coated pits and vesicles. In what follows, we review the current state of knowledge of the clathrin-dependent pathway. Specific primary references to the work cited here can be found in the published reviews listed at the end of this lecture notes.