The COPI system: Molecular mechanisms and function

Abstract

a b s t r a c tTransport of membranes and proteins in eukaryotic cells is mediated by vesicular carriers. Here we review the biogenesis and functions of COPI vesicles, carriers that operate in the early secretory pathway. We focus on mechanisms mediating coat recruitment, uptake of cargo, vesicle budding and fission, and finally dissociation of the coat. In this context, recent findings on the interplay between machinery and auxiliary proteins in COPI vesicle formation and function will be discussed. Specifically, we will weigh the pros and cons of recent data on roles of the small GTP binding protein Arf1, of Arf1GAPs, and lipids during COPI carrier formation.

ArfGAP1 promotes COPI vesicle formation by facilitating coatomer polymerization

“…While our results contrast with previously reported results 18,28,29,34,35,39,58 in which it was reported that Arf1 and coatomer were sufficient for vesicle formation, they do not necessarily contradict these studies. The population of LUVs generated by the extrusion method, which is a frequently used method that we used in this work, contains many vesicles with diameters between 30 and 150 nm.…”

“…Two opposing models are currently debated. 4,17,18,34,37,38,48 In one model, ArfGAP1 acts as a negative regulator of the GTP-binding protein Arf, preventing formation of vesicles and/or triggering coat dissociation from vesicles. In a second model, ArfGAP1 has a positive role for the formation of vesicles.…”

“…The conversion of Arf1•GDP to Arf1•GTP results in the recruitment of coatomer to membranes containing cargo. 4,17,18 Coatomer binds to cargo and then polymerizes into COPI, which deforms the membrane into a bud. The coated bud undergoes fission to…”

Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain

“…In order to understand the molecular mechanisms of SM 18 enrichment in vesicles, we investigated in vivo binding of lipids to p24 and p23, membrane proteins involved in COPI vesicle biogenesis ( Supplementary Fig. 1) 6 . Lipid crosslinking 7,8 revealed a strong sphingolipid labelling of p24 (Fig.…”

RNA interference mediated knockdown of the KDEL receptor and COPB2 inhibits digestion and reproduction in the parasitic copepod Lepeophtheirus salmonis

“…Resident ER proteins interact directly with the COPI subunits, by interaction with a Vps74p linker, or by binding to the KDEL receptor (KDELR) (reviewed by Beck et al, 2009;Bethune et al, 2006;Szul and Sztul, 2011). Proteins with a C-terminal KDEL motif (HDEL in yeast) are recognized by KDELR, also known as the ER lumen retaining protein receptor (ERPR).…”