Academic journal article Genetics

Traffic through the Trans-Golgi Network and the Endosomal System Requires Collaboration between Exomer and Clathrin Adaptors in Fission Yeast

Academic journal article Genetics

Traffic through the Trans-Golgi Network and the Endosomal System Requires Collaboration between Exomer and Clathrin Adaptors in Fission Yeast

Article excerpt

THE Golgi is a sorting node from where proteins are delivered to their final destinations following a retrograde route to the endoplasmic reticulum, or anterograde routes to the cell surface and to the vacuoles through the endosomal system. Additionally, there is direct traffic fromthe Golgi to the vacuoles. Different coats and adaptors facilitate trafficking between cell compartments (Lemmon and Traub 2000; De Matteis and Luini 2008; Anitei and Hoflack 2011; Barlowe and Miller 2013; Guo et al. 2014). Trafficking from the Golgi to the plasma membrane (PM) is less well-understood than other protein transport processes, such as trafficking from the endoplasmic reticulum to the Golgi or endocytosis (Spang 2015). It is known that a variety ofmembranous carriers transport different proteins fromthe Golgi to specialized domains of the PM (De Matteis and Luini 2008). While clathrin and the Assembly Polypeptide adaptor 1 (AP-1) are required for the packaging of some cargoes into carriers, other coats and adaptors participate in cargo sorting. Furthermore, inmany cases, it has not been determined whether carriers bear specific receptors, adaptors, or coats (De Matteis and Luini 2008; Wakana et al. 2012; Bonifacino 2014; Spang 2015). Alterations in Golgi function and protein secretion are associated with human disease (Tang 2009; Bexiga and Simpson 2013). Therefore, the characterization of protein complexes acting in protein trafficking from the Golgi to the cell surface is of considerable biological and medical relevance.

Clathrin and AP-1 participate in the traffic between the trans-Golgi network (TGN) and early endosomes (EEs), and contribute to the retention of some proteins, including the Saccharomyces cerevisiae chitin synthase Chs3 and murine mannose-6-phosphate receptor, at the TGN (Meyer et al. 2000; Valdivia et al. 2002). The clathrin adaptor AP-2 participates in clathrin-mediated endocytosis, delivering proteins from the PM to the EEs, from where proteins can be sorted to the PM and to the Golgi. Additionally, EEs maturate into late endosomes (LEs) that produce multivesicular bodies (MVBs), which fuse to the lysosomes (vacuoles in yeast) (Huotari and Helenius 2011). In yeast, the term prevacuolar compartment (PVC) includes the LEs and MVBs (Scott et al. 2014). Protein trafficking from the Golgi to the PVC requires the participation of GGA (Golgi-localized, Gamma-adaptin ear domain homology, ARF-binding) adaptors. Although GGAs mediate transport from the TGN to the PVC, both in mammals and budding yeast, they also interact and colocalize with EE proteins. Furthermore, budding yeast GGAs contribute to Chs3 cycling between the TGN and EEs, and participate in the cycling of the synaptobrevin-related protein Snc1 between the PM and EEs (Black and Pelham 2000; Doray et al. 2002; Copic et al. 2007; Hirst et al. 2012). Direct trafficking from the Golgi to the vacuoles requires AP-3.

Exomer mediates the transport of a subset of transmembrane cargoes from the TGN/EEs to the PM in S. cerevisiae (Santos and Snyder 1997, 2003; Ziman et al. 1998; Barfield et al. 2009; Ritz et al. 2014). It is a heterotetramer consisting of any two ChAPs (Chs5p-Arf1p-binding Proteins; Bch1, Bud7, Chs6, and Bch2) and two copies of the scaffold Chs5 (Sanchatjate and Schekman 2006; Trautwein et al. 2006; Wang et al. 2006; Paczkowski and Fromme 2014; Huranova et al. 2016). The best-characterized role of exomer is Chs3 trafficking from the Golgi to the PM. In exomer-deficient mutants, Chs3 is retained in an intracellular compartment that exhibits characteristics of TGN and EEs (Santos and Snyder 1997; Ziman et al. 1998; Sanchatjate and Schekman 2006; Trautwein et al. 2006). As a consequence, cells are defective in the synthesis of the cell wall, the fungal counterpart of the extracellular matrix. AP-1 disruption in exomer mutants allows Chs3 rerouting to the PMthrough an alternative pathway, showing a functional relationship between exomer and this clathrin adaptor for chitin synthesis (Valdivia et al. …

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