The multiple facets of the Golgi reassembly stacking proteins

Abstract

The mammalian GRASPs (Golgi reassembly stacking proteins) GRASP65 and GRASP55 were first discovered more than a decade ago as factors involved in the stacking of Golgi cisternae. Since then, orthologues have been identified in many different organisms and GRASPs have been assigned new roles that may seem disconnected. In vitro, GRASPs have been shown to have the biochemical properties of Golgi stacking factors, but the jury is still out as to whether they act as such in vivo. In mammalian cells, GRASP65 and GRASP55 are required for formation of the Golgi ribbon, a structure which is fragmented in mitosis owing to the phosphorylation of a number of serine and threonine residues situated in its C-terminus. Golgi ribbon unlinking is in turn shown to be part of a mitotic checkpoint. GRASP65 also seems to be the key target of signalling events leading to re-orientation of the Golgi during cell migration and its breakdown during apoptosis. Interestingly, the Golgi ribbon is not a feature of lower eukaryotes, yet a GRASP homologue is present in the genome of Encephalitozoon cuniculi, suggesting they have other roles. GRASPs have no identified function in bulk anterograde protein transport along the secretory pathway, but some cargo-specific trafficking roles for GRASPs have been discovered. Furthermore, GRASP orthologues have recently been shown to mediate the unconventional secretion of the cytoplasmic proteins AcbA/Acb1, in both Dictyostelium discoideum and yeast, and the Golgi bypass of a number of transmembrane proteins during Drosophila development. In the present paper, we review the multiple roles of GRASPs.

Functional Characterization of Monomeric GTPase Rab1 in the Secretory Pathway of Leishmania

“…GRASP (Golgi reassembly stacking protein) is the single Drosophila homolog of mammalian GRASP55 and GRASP65. These two proteins have been shown to be localized only to the Golgi, and they play a role in Golgi organization (58,59). Subsequently, it has been shown that ␣PS1 integrins in Drosophila are secreted in a Golgi-independent fashion but are dependent on GRASP.…”

Architecture of the Mammalian Golgi

“…Recent studies indicate that the formation of a Golgi ribbon is particularly important for protein glycosylation. The Golgi ReAssembly Stacking Proteins GRASP65 and GRASP55 function in the formation and/ or maintenance of the tubules connecting the Golgi stacks, presumably by forming protein tethers between adjacent membranes (Barr et al 1998;Shorter et al 1999;Rabouille and Kondylis 2007;Feinstein and Linstedt 2008;Vinke et al 2011 This results in the redistribution of Golgi enzymes over the stacks and affects proper protein glycosylation, but does not cause a block in secretion (Puthenveedu et al 2006;Marra et al 2007b). It remains to be established, however, whether GM130 acts directly in homotypic fusion of neighboring cisternae (Puthenveedu et al 2006) or mediates the tethering of ER-derived vesicles with the cis-Golgi (Marra et al 2007a).…”

JNK2 controls fragmentation of the Golgi complex and the G2/M transition through phosphorylation of GRASP65

“…This homotypic trans-oligomerisation is required for the formation of the Golgi stacks, and also for the 'lateral' connections between homotypic cisternae to promote the formation of the Golgi ribbon. The trans-oligomerisation is inhibited by phosphorylation events at the C-terminal halves of these proteins (for a review, see Vinke et al, 2011).…”