Role of tethering factors in secretory membrane traffic

Abstract

Sztul, Elizabeth, and Vladimir Lupashin. Role of tethering factors in secretory membrane traffic. Am J Physiol Cell Physiol 290: C11-C26, 2006; doi:10.1152/ ajpcell.00293.2005.-Coiled-coil and multisubunit tethers have emerged as key regulators of membrane traffic and organellar architecture. The restricted subcellular localization of tethers and their ability to interact with Rabs and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) suggests that tethers participate in determining the specificity of membrane fusion. An accepted model of tether function considers them molecular "bridges" that link opposing membranes before SNARE pairing. This model has been extended by findings in various experimental systems, suggesting that tethers may have other functions. Recent reports implicate tethers in the assembly of SNARE complexes, cargo selection and transit, cytoskeletal events, and localized attachment of regulatory proteins. A concept of tethers as scaffolding machines that recruit protein components involved in varied cellular responses is emerging. In this model, tethers function as integration switches that simultaneously transmit information to coordinate distinct processes required for membrane traffic. membrane tethering INTENSE INVESTIGATION over the past few decades has produced a general framework of the organelles and the factors regulating cargo transport from the endoplasmic reticulum (ER) to the plasma membrane (PM). Initial electron microscopic studies and more recent usage of light and live imaging have identified secretory compartments that handle cargo as it travels to the cell surface. All secretory and transmembrane proteins enter the pathway at the ER and are then sequentially transported through the ER-Golgi intermediate compartment (ERGIC), the Golgi complex, and the trans-Golgi network (TGN) before reaching the PM. Transport between the compartments occurs through small vesicles or larger tubulovesicular and tubular structures.In all cases, cargo is selected from the donor compartment by being sorted into a vesicle or a larger intermediate that then detaches from the donor compartment. The separation of cargo from resident proteins is mediated by the spatially restricted recruitment of coats. All coats studied to date are recruited to membranes by the active GTP-bound forms of the Sar1/ARF family of small GTPases (reviewed in Ref. 14). The recruitment of the coat is coupled to the sorting of the cargo into a transport intermediate. The sorting of cargo for export from the ER is mediated by the coat protein complex II (COPII) and the Sar1 GTPase. The sorting of cargo for exit from the TGN is mediated by clathrin and the ARF and Arl GTPases. An additional COPI coat recruited by ARF mediates protein sorting at the ERGIC and the Golgi. Available evidence indicates that COPI mediates the recycling of cellular components and does not directly participate in cargo sorting.After budding from the donor compartment, the transport intermediates traverse a certain distan...

Isolation and proteomic analysis of the SYP61 compartment reveal its role in exocytic trafficking in Arabidopsis

“…During vesicle fusion, tethering factors, such as the transport protein particle (TRAPPI and TRAPPII) complexes, function upstream of SNAREs, acting over long distances to bring the interacting complexes together and to provide additional compartment specificity [36]. The SYP61 proteome contained a Trs120 homolog, a member of the TRAPPII complex with a putative role in cytokinesis [37].…”

Minimal membrane docking requirements revealed by reconstitution of Rab GTPase-dependent membrane fusion from purified components

“…Tethering may be mediated by ''tethering factors'' that interact simultaneously with binding partners, including Rab proteins, in apposed membranes (9,(54)(55)(56)(57). However, no proposed Rab-dependent tethering factor has ever, to our knowledge, been shown to have direct membrane-bridging activity in a chemically defined membrane tethering reaction.…”

COG-7-deficient Human Fibroblasts Exhibit Altered Recycling of Golgi Proteins

“…In contrast, a role for the COG complex in trafficking events between the endoplasmic reticulum (ER) and Golgi is less established (Sztul and Lupashin, 2006). Studies in COGdeficient yeast mutants suggest that COG may play a role in ER export and ER-to-Golgi transport (VanRheenen et al, 1998(VanRheenen et al, , 1999Morsomme et al, 2003).…”

“…Because resident Golgi proteins such as glycosylation enzymes are known to recycle within the Golgi stack and between the Golgi and ER, these findings support the general hypothesis that altered trafficking of these proteins results in their mislocalization, altered activity, possible degradation, or a combination. Indeed, a role for the COG complex in controlling the abundance of a subset of Golgi proteins (including glycosylation enzymes) in Chinese hamster ovary (CHO) cells has been recently demonstrated by Krieger and colleagues (Oka et al, 2004).In contrast, a role for the COG complex in trafficking events between the endoplasmic reticulum (ER) and Golgi is less established (Sztul and Lupashin, 2006). Studies in COGdeficient yeast mutants suggest that COG may play a role in ER export and ER-to-Golgi transport (VanRheenen et al, 1998(VanRheenen et al, , 1999Morsomme et al, 2003).…”