BIOSYNTHETIC PROTEIN-TRANSPORT THROUGH THE EARLY SECRETORY PATHWAY

Newly synthesized proteins destined for delivery to the cell surface a re inserted cotranslationally into the endoplasmic reticulum (ER) and, after their correct folding, are transported out of the ER. During th eir transport to the cell surface, cargo proteins pass through the var ious cisternae of the Golgi apparatus and, in the trans-most cisternae of the stack, are sorted into constitutive secretory vesicles that fu se with the plasma membrane. Simultaneously with anterograde protein t ransport, retrograde protein transport occurs within the Golgi complex as well as from the Golgi back to the ER. Vesicular transport within the early secretory pathway is mediated by two types of non-clathrin c oated vesicles: COPI- and COPII-coated vesicles. The formation of thes e carrier vesicles depends on the recruitment of cytosolic coat protei ns that are thought to act as a mechanical device to shape a flattened donor membrane into a spherical vesicle. A general molecular machiner y that mediates targeting and fusion of carrier vesicles has been iden tified as well. Beside a general overview of the various coat structur es known today, we will discuss issues specifically related to the bio genesis of COPI-coated vesicles: (1) a possible role of phospholipase D in the formation of COPI-coated vesicles; (2) a functional role of a novel family of transmembrane proteins, the p24 family, in the initia tion of COPI assembly; and (3) the direction COPI-coated vesicles may take within the early secretory pathway. Moreover, we will consider tw o alternative mechanisms of protein transport through the Golgi stack: vesicular transport versus cisternal maturation.