Multisubunit Tethering Complexes and Their Role in Membrane Fusion

Abstract

Protein trafficking within eukaryotic cells depends on vesicular carriers that fuse with organelles to deliver their lipid and protein content. Cells have developed an elaborate system to capture vesicles at organelles that involves the action of Rab GTPases and tethers. Vesicle fusion then takes place with the help of SNARE proteins. In this review we focus on the role of multisubunit tethering complexes of eukaryotic cells. In particular, we discuss the tethering complexes of the secretory pathway and the endolysosomal system and highlight recent evidence for the role of these complexes in interaction with Rabs, coat recognition and cooperation with SNAREs during the fusion cascade.

Guanine Nucleotide Exchange Factors (GEFs) Have a Critical but Not Exclusive Role in Organelle Localization of Rab GTPases

“…It is thus unlikely that a potential GFP-induced oligomerization of GFP-Ypt7 affects the subcellular distribution of Ypt7. Human Rab7, which requires the human Mon1-Ccz1 complex for localization, 3 behaved like Ypt7 in GEF deletion strains (supplemental Fig. S1B).…”

“…SNAREs fold in a zipper-like manner into tight four-helix complexes. This brings the two membranes into close contact and thus mediates bilayer mixing (1)(2)(3). The main regulation of membrane fusion appears to occur at the level of Rabs and tethering proteins.…”

Rab GTPases and tethering in the yeast endocytic pathway

“…Whether this occurs sequentially or concomitantly and who comes first is a most interesting open question. 1,3,4 Among the five principal families of small GTPases the Rabs ["Ras" = (Rat sarcoma)-related in brain] are central regulators of vesicle budding, motility, and fusion. They also comprise the largest number: 11 in S. cerevisiae, > 60 in humans, and close to 60 in Arabidopsis thaliana.…”

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

“…For this they require tethers. Tethers function as flexible molecular bridges linking the two membranes, thereby contributing to cargo selection and cytoskeletal interactions, as well as the localization and assembly of the soluble NSF attachment protein (SNAP) receptor (SNARE) complexes that are necessary for membrane fusion (Sztul and Lupashin, 2006;Wu et al, 2008;Bröcker et al, 2010). The best-known tethering complex at the plasma membrane is the exocyst.…”