The Secret Life of Tethers: The Role of Tethering Factors in SNARE Complex Regulation

Abstract

Trafficking in eukaryotic cells is a tightly regulated process to ensure correct cargo delivery to the proper destination organelle or plasma membrane. In this review, we focus on how the vesicle fusion machinery, the SNARE complex, is regulated by the interplay of the multisubunit tethering complexes (MTC) with the SNAREs and Sec1/Munc18 (SM) proteins. Although these factors are used in different stages of membrane trafficking, e.g., Golgi to plasma membrane transport vs. vacuolar fusion, and in a variety of diverse eukaryotic cell types, many commonalities between their functions are being revealed. We explore the various protein-protein interactions and findings from functional reconstitution studies in order to highlight both their common features and the differences in their modes of regulation. These studies serve as a starting point for mechanistic explorations in other systems.

Keywords: SNARE complexes; Sec1/Munc18; intracellular trafficking; multisubunit tethering complexes.

Figure 1

Overview depicting MTC localization in yeast. The various subcellular locations and trafficking pathways in yeast are depicted, along with the tethering complexes associated with each pathway. The TRAPPI complex is involved in ER to cis-Golgi traffic, with the Dsl1 complex required for retrograde Golgi to ER traffic. The TRAPPII and COG complexes are involved in retrograde Golgi traffic between the various Golgi compartments. CORVET functions in both trans-Golgi to early endosome trafficking and early endosome to MVB/late endosome trafficking. The HOPS complex is required for MVB/late endosome to vacuole/lysosome vesicle fusion. Early endosome to Golgi recycling requires the GARP complex, while Golgi to plasma membrane trafficking requires the exocyst complex. Each of the pathways depicted have associated SNARE proteins; the tether-SNARE interactions discussed in this review are outlined in Table 1. The role of TRAPPIII in autophagosome formation is not shown. ER, endoplasmic reticulum; MVB, multivesicular body/late endosome.