PMC:4635215 / 3414-6984 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4635215","sourcedb":"PMC","sourceid":"4635215","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4635215","text":"Golgi disassembly and stress\nGolgi fragmentation is commonly observed in cells subjected to “stress,” including pharmacological and oxidative stress. Fragmentation can be the result of perturbation of microtubules, or phosphorylation or cleavage of Golgi structural proteins. Golgi stacks can be dispersed (mini-stacks) or completely disassembled, depending on the perturbation (Figure 1B). Although the term “Golgi stress” has been frequently used in the literature (e.g., Jiang et al., 2011; Oku et al., 2011; Reiling et al., 2013), there is no clear understanding of what Golgi stress entails. Can Golgi stress be activated in the absence of endoplasmic reticulum (ER) stress? Similar to the well-documented unfolded protein response in the ER (Walter and Ron, 2011), a Golgi stress response pathway should serve to help alleviate the stress, and only result in cell death if the stress is irreparable (Figure 1C). Pharmacological inhibitors of glycosyltransferases, glycosidases, proton and calcium pumps, and perturbation of luminal pH have all been shown to alter the structure of the Golgi complex. High levels of cargo or large cargo passing through the Golgi may be the most physiological type of stress. But do any of these insults result in outcomes that would help eliminate the stress?\nOne of the most extensively studied types of cellular stress is pro-apoptotic stress. In apoptosis, extrinsic, or intrinsic pathways lead to programmed disassembly of the cell. Cysteine proteases called caspases are activated and cleave a select set of cellular proteins during programmed cell death. Different types of stress activate specific initiator caspases, which then activate effector caspases (Boatright and Salvesen, 2003). Not all caspases are involved in cell death however.\nWe previously reported that procaspase-2 is partially localized at the cytoplasmic face of the Golgi complex (Mancini et al., 2000), and golgin-160 and several other golgins are caspase-2 substrates (Mancini et al., 2000; Lowe et al., 2004). Caspase cleavage of golgin-160 is predicted to inhibit its function in promoting efficient trafficking of specific cargo molecules (Bundis et al., 2006; Hicks et al., 2006; Williams et al., 2006). Caspase-2 is an unusual caspase in that it possesses a long prodomain like inititator caspases, but does not activate effector caspases (Fava et al., 2012). Recent evidence suggests non-apoptotic roles for caspase-2 in maintaining genome stability, checkpoint regulation in the cell cycle, response to oxidative stress, tumor suppression and in aging (Olsson et al., 2015).\nAnother stress that acts at the Golgi complex is inhibition of O-glycosylation. It was shown that treatment of fibroblasts with benzyl 2-acetamido-2-deoxy-a-d-galactopyranoside (GalNAc-bn) to inhibit this post-translational modification induced upregulation of HSP47, an ER chaperone (Miyata et al., 2013). HSP47 apparently protects cells from Golgi fragmentation and death when O-glycosylation is blocked because knock-down of HSP47 in GalNAc-bn treated cells led to Golgi vacuolization and eventual apoptosis. Interestingly, caspase-2 appears to be activated here as well. The mechanism by which HSP47 leads to protection is unknown, but it has been reported to be a collagen-specific chaperone (Mala and Rose, 2010). HSP47 may regulate the level of this abundant secretory protein that enters the Golgi, whereas in its absence collagen might accumulate in the Golgi when it cannot be O-glycosylated, resulting in Golgi structural perturbations and eventual 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