Architectural editing: determining the fate of newly synthesized membrane proteins

Abstract

Many integral membrane proteins exist on the plasma membrane as part of multicomponent complexes. In addition to correctly transporting newly synthesized proteins from their site of synthesis in the endoplasmic reticulum to the plasma membrane, the cell must possess mechanisms to ensure that the complexes expressed on the cell surface are accurately assembled. The cell appears to accomplish this feat by superimposing a set of constraints on the newly synthesized membrane proteins whereby the structure and state of assembly of the protein determine its intracellular fate. These processes impose a dramatic level of post-translational regulation on the expression of surface membrane protein complexes. By and large, the cell uses these mechanisms to dispose of, or "edit out," newly synthesized proteins that are not correctly assembled or folded. This review will describe current views of the processes of architectural editing, with an emphasis on the regulation of cell surface expression of the multicomponent T-cell antigen receptor complex.