The Golgin Family of Coiled-Coil Tethering Proteins

Abstract

The golgins are a family of predominantly coiled-coil proteins that are localized to the Golgi apparatus. Golgins are present in all eukaryotes, suggesting an evolutionary conserved function. Golgins are anchored to the Golgi membrane by their carboxy terminus and are predicted to adopt an extended conformation that projects into the surrounding cytoplasm. This arrangement is ideal for the capture or tethering of nearby membranes or cytoskeletal elements. Golgin-mediated tethering is thought to be important for vesicular traffic at the Golgi apparatus, the maintenance of Golgi architecture, as well as the positioning of the Golgi apparatus within cells. In addition to acting as tethers, some golgins can also sequester various factors at the Golgi membrane, allowing for the spatiotemporal regulation of downstream cellular functions. Although it is now established that golgins are membrane and cytoskeleton tethers, the mechanisms underlying tethering remain poorly defined. Moreover, the importance of golgin-mediated tethering in a physiological context remains to be fully explored. This review will describe our current understanding of golgin function, highlighting recent progress that has been made, and goes on to discuss outstanding questions and potential avenues for future research with regard to this family of conserved Golgi-associated proteins.

Keywords: Golgi apparatus; cytoskeleton; golgin; tether; vesicle trafficking.

Figure 1

Topology and membrane attachment of golgins. Golgins are comprised predominantly of coiled-coil regions (depicted by black helices; note that the frequent short breaks found within the coiled-coil regions of golgins are not shown for simplicity). Golgins can either be directly anchored to the Golgi membrane through carboxy-terminal transmembrane domains (giantin, golgin-84 and CASP), or they can associate with the Golgi membrane through interactions with other Golgi-localized proteins. The carboxy-terminus of GM130 acts as a ligand for the PDZ domains of GRASP65. Trans-Golgi golgins have a GRIP domain that interacts with Arl1, whereas GMAP-210 has an analogous GRAB domain that binds to Arf1. TMF and golgin-160 are attached to the Golgi membrane via binding of their carboxy-terminal regions to Rab6 or Arf1 respectively.

Figure 2

Model for vesicle tethering by the golgin GMAP-210. Vesicles are specifically recognized and captured at the cis-Golgi by the amino-terminal ALPS motif (red). Bound vesicles can be transferred to a neighboring golgin(s) through additional vesicle attachment sites present on the neighboring golgin(s). Alternatively, the presence of other vesicle attachment sites on the same golgin will allow transport of vesicles along the same golgin molecule. In the case of GMAP-210, the vesicle attachment site is a Rab2-binding site, allowing binding to vesicle-associated Rab2. Movement onto the secondary vesicle attachment sites will bring the vesicle into closer proximity with the Golgi membrane to promote fusion there. GMAP-210 may also undergo a conformational change to bring the vesicle into closer proximity to the Golgi membrane, as shown on the left.

Figure 3

Regulation of golgin function in mitosis and apoptosis. Golgins primarily act as vesicle tethers at the Golgi apparatus. In mitosis, golgins undergo phosphorylation mediated by protein kinases, which impairs vesicle tethering by preventing interaction with binding partners e.g., p115 binding to GM130, or by disassociation of the golgin from the Golgi membrane e.g., golgin-160. In apoptosis, activated caspases cleave golgins leading to their release from the Golgi e.g., GM130, or their extensive trimming e.g., golgin-160. Phosphorylation or cleavage of golgins prevents vesicle tethering, leading to conversion of cisternal membrane to vesicles and Golgi apparatus disassembly.