Biosynthetic protein transport through the early secretory pathway

Abstract

Newly synthesized proteins destined for delivery to the cell surface are inserted cotranslationally into the endoplasmic reticulum (ER) and, after their correct folding, are transported out of the ER. During their transport to the cell surface, cargo proteins pass through the various cisternae of the Golgi apparatus and, in the trans-most cisternae of the stack, are sorted into constitutive secretory vesicles that fuse with the plasma membrane. Simultaneously with anterograde protein transport, 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 coated vesicles: COPI- and COPII-coated vesicles. The formation of these carrier vesicles depends on the recruitment of cytosolic coat proteins that are thought to act as a mechanical device to shape a flattened donor membrane into a spherical vesicle. A general molecular machinery that mediates targeting and fusion of carrier vesicles has been identified as well. Beside a general overview of the various coat structures known today, we will discuss issues specifically related to the biogenesis 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 initiation of COPI assembly; and (3) the direction COPI-coated vesicles may take within the early secretory pathway. Moreover, we will consider two alternative mechanisms of protein transport through the Golgi stack: vesicular transport versus cisternal maturation.

Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100–Containing Lipoproteins

“…ARF1 and COPI are important for the sorting and transport of proteins from the ER to the Golgi apparatus. 15,16,21 Thus, ARF1 could promote the transfer of pre-VLDL from the site of synthesis in the rough ER to the smooth membrane compartment, where the second step occurs. 10 Like other secreted proteins, apoB-100 in a non-VLDL form leaves the ER in Sar1/COPII vesicles, 22 which participate in the formation of ERGIC.…”

“…Activation of ARF1 initiates the binding of COP I to the membrane of the secretory pathway, an important step in the formation of transport vesicles and ARF1/COPIdependent sorting events. 15,16,21 Because the ERGIC must interact with COPI before it can be transported to the cis-Golgi, 23,24 the effect of T31N ARF 1 on VLDL 1 assembly may reflect inhibition of anterograde transport. Such a mechanism is supported by our observation that the inhibition of VLDL 1 assembly coincided with the loss of transfer of VSV-G protein from the ER to the Golgi.…”

Structure and function of the notochord: an essential organ for chordate development

“…Seven coatomer subunits, in combination with the small GTPase Arf1, make up the coat of COPI vesicles (Bannykh et al, 1998;Cosson and Letourneur, 1997;Lowe and Kreis, 1998;Nickel and Wieland, 1998). In eukaryotic cells, there are at least three vesicular coating systems.…”

Surface Expression of Inward Rectifier Potassium Channels Is Controlled by Selective Golgi Export

“…Thus, the C-terminal amino acid sequence YXX⌽ (with X being any amino acid and ⌽ being a bulky, hydrophobic residue) or di-leucine motifs favor clathrin-mediated endocytosis of membrane proteins (9), C-terminal di-lysine motifs have been shown to bind COPI (15), and a growing number of N-and C-terminal diacidic motifs render selective ER export, most likely by binding to COPII coat complexes (16 -19). However, it is still a matter of debate whether sequence information also facilitates protein transport between the Golgi compartment and the cell surface or whether this step of the secretory pathway is constitutive (20,21).…”