Sequential interactions with Sec23 control the direction of vesicle traffic

Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0668, USA.
Nature (Impact Factor: 41.46). 05/2011; 473(7346):181-6. DOI: 10.1038/nature09969
Source: PubMed


How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1δ orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.

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Available from: Majid Ghassemian, Oct 04, 2015
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    • "It is possible that during budding and/or just before completion, at least partial portion of the Sar1/Arf1 proteins were released from the membrane surface of coated vesicles by the action of GAP. This fits with the observation that the TRAPPI complex and Ypt1, which serve in the tethering event, can bind to COPII vesicles through the interaction with Sec23 after Sar1 is depleted (Cai et al., 2007; Lord et al., 2011). Subsequently, at the Golgi surface, the Hrr25 protein kinase, in association with the Golgi, phosphorylates Sec23/24 to release the coat and eventually promote vesicle fusion. "
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    ABSTRACT: Small GTPase proteins play essential roles in the regulation of vesicular trafficking systems in eukaryotic cells. Two types of small GTPases, secretion-associated Ras-related protein (Sar) and ADP-ribosylation factor (Arf), act in the biogenesis of transport vesicles. Sar/Arf GTPases function as molecular switches by cycling between active, GTP-bound and inactive, GDP-bound forms, catalyzed by guanine nucleotide exchange factors and GTPase-activating proteins, respectively. Activated Sar/Arf GTPases undergo a conformational change, exposing the N-terminal amphipathic α-helix for insertion into membranes. The process triggers the recruitment and assembly of coat proteins to the membranes, followed by coated vesicle formation and scission. In higher plants, Sar/Arf GTPases also play pivotal roles in maintaining the dynamic identity of organelles in the secretory pathway. Sar1 protein strictly controls anterograde transport from the endoplasmic reticulum (ER) through the recruitment of plant COPII coat components onto membranes. COPII vesicle transport is responsible for the organization of highly conserved polygonal ER networks. In contrast, Arf proteins contribute to the regulation of multiple trafficking routes, including transport through the Golgi complex and endocytic transport. These transport systems have diversified in the plant kingdom independently and exhibit several plant-specific features with respect to Golgi organization, endocytic cycling, cell polarity and cytokinesis. The functional diversification of vesicular trafficking systems ensures the multicellular development of higher plants. This review focuses on the current knowledge of Sar/Arf GTPases, highlighting the molecular details of GTPase regulation in vesicle formation in yeast and advances in knowledge of the characteristics of vesicle trafficking in plants.
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    • "Consistent with their functional importance, we recently confirmed that the C-terminal tail of TgSORTLR binds specifically to the cytosolic sorting complexes involved in anterograde transport or retrograde transport [45]. For anterograde transport, the TgSORTLR cytoplasmic tail not only binds clathrin and to three components of the AP1 and AP2 adaptor complexes, but also to homologues of Vps9 and of the COPII or coat complex transport proteins Sec23/Sec24 that ensure the directionality of anterograde membrane flow from the ER to the Golgi apparatus [47]. For retrograde transport, TgSORTLR binding to Vps26-Vps29-Vps35 indicated its association with the retromer complex, which mediates transport from endosomes to the trans-Golgi network. "
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    • "As an example, PKA phosphorylates CKId both in vitro and in vivo, predominantly on Ser370, and this site-specific phosphorylation of CKId has an important role in positive modulation of CK1d-dependent processes (Giamas et al. 2007). The disengaging of the SNAREs from the COPII coat at the Golgi complex by phosphorylation of Sec24p by CKId (Lord et al. 2011) probably prevents the fusion of COPII vesicles with the ER (Lord et al. 2011). The syntaxins are phosphorylated by CKI on Thr21 (Dubois et al. 2002), although this phosphorylation has only been seen in vitro. "
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