Assembly of cell membranes

Abstract

The current state of knowledge concerning the mechanisms of assembly of membranes in animal cells will be reviewed. Assembly mechanisms must be able to account for the generation and maintenance of the unique composition of each subcellular compartment, and also for general structural properties of all membranes such as membrane-spanning proteins and the asymmetrical arrangement of oligosaccharide chains. Assembly is accomplished in a multistage process involving two major organelles, the endoplasmic reticulum (ER) and the Golgi apparatus, which appear to be specialized for these purposes. Proteins destined for diverse subcellular compartments (such as plasma membrane, secretion storage granules, and lysosomes) are synthesized by ribosomes attached to the ER and are deposited as a mixture into the lumen or membrane of the ER. These proteins are typically glycoproteins, and their Asn-linked oligosaccharides are added contranslationally by enzymatic machinery located on the lumenal face of the ER membrane. These precursors to other organelles are then transported into the stack of cisternae of the Golgi, arriving at one end (the "cis" face) and exiting from the other (the "trans" face). During their transit across the Golgi they pass through a series of distinct subcompartments, within which characteristic stages in the remodeling of their oligosaccharide chains occur. The actual separation or sorting of precursors according to final subcellular destination occurs in the last (trans-most) Golgi cisterna; proteins destined for lysosomes, secretions, and plasma membranes are believed to be packaged into different vesicles that bud from the trans Golgi. To permit to the kinds of specific intercompartmental transport that underlies this protein sorting process, (1) transported proteins must have "sorting signals" to specify their destination; (2) cognate receptors must exist in the ER and Golgi to effect this recognition; and (3) vesicles moving between compartments must package such receptors together with their cognate proteins but exclude other proteins as they bud. Examples of sorting signals and sorting receptors will be discussed, as will be the properties of clathrin-coated pits and coated vesicles, that are believed to provide a general mechanism for intercompartmental transfer of selected sets of membrane proteins.