Tethering

Abstract: Despite the recent progress in the field of membrane traffic, the question of how the specificity of membrane fusion is achieved has yet to be resolved. It has become apparent that the SNARE proteins, although central to the process of fusion, are often not the first point of contact between a vesicle and its target. Instead, a poorly understood tethering process physically links the two before fusion occurs. Many factors that have an apparent role in tethering have been identified. Among these are several large protein complexes. Until recently, these seemed unrelated, which was a surprise since proteins involved in membrane traffic often form families, members of which function in each transport step. Recent work has shown that three of the complexes are in fact related. We refer to these as the `quatrefoil9 tethering complexes, since they appear to share a fourfold nature. Here we describe the quatrefoil complexes and other, unrelated, tethering complexes, and discuss ideas about their function. We propose that vesicle tethering may have separate kinetic and thermodynamic elements and that it may be usefully divided into events upstream and downstream of the function of Rab GTPases. Moreover, the diversity of tethering complexes in the cell suggests that not all tethering events occur through the same mechanisms.

Abstract: Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

Abstract: Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the CORVET complex, while fusion of late endosomes with lysosomes depends on the HOPS complex. Recycling through the TGN and to the plasma membrane is facilitated by the GARP and EARP complexes, respectively. However, there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, complexes that may be part of novel tethering complexes have been recently identified. Thus it is likely that more tethering factors exist. In this review, I will provide an overview of different tethering complexes of the endosomal system and discuss how they may provide specificity in membrane traffic.

Abstract: We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks.