Secretory Pathway Quality Control Operating in Golgi, Plasmalemmal, and Endosomal Systems

Arvan, Peter; Zhao, Xiang; Ramos‐Castañeda, José; Chang, Amy

doi:10.1034/j.1600-0854.2002.31102.x

Cited by 183 publications

(171 citation statements)

References 97 publications

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“…The ER is the site for the maturation of secretory and membrane proteins, and improperly folded or excess proteins are frequently retained in the ER and subjected to ER-associated protein degradation (Arvan et al, 2002;Hegde and Ploegh, 2010). Recently, interplay between protein phosphorylation and ubiquitination in ER-associated protein degradation was demonstrated .…”

Section: A Ck2-integrated Model For Pt Er Exitmentioning

confidence: 99%

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

et al. 2015

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Phosphate transporters (PTs) mediate phosphorus uptake and are regulated at the transcriptional and posttranslational levels. In one key mechanism of posttranslational regulation, phosphorylation of PTs affects their trafficking from the endoplasmic reticulum (ER) to the plasma membrane. However, the kinase(s) mediating PT phosphorylation and the mechanism leading to ER retention of phosphorylated PTs remain unclear. In this study, we identified a rice (Oryza sativa) kinase subunit, CK2b3, which interacts with PT2 and PT8 in a yeast two-hybrid screen. Also, the CK2a3/b3 holoenzyme phosphorylates PT8 under phosphate-sufficient conditions. This phosphorylation inhibited the interaction of PT8 with PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1, a key cofactor regulating the exit of PTs from the ER to the plasma membrane. Additionally, phosphorus starvation promoted CK2b3 degradation, relieving the negative regulation of PT phosphorus-insufficient conditions. In accordance, transgenic expression of a nonphosphorylatable version of OsPT8 resulted in elevated levels of that protein at the plasma membrane and enhanced phosphorus accumulation and plant growth under various phosphorus regimes. Taken together, these results indicate that CK2a3/b3 negatively regulates PTs and phosphorus status regulates CK2a3/b3.

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Section: A Ck2-integrated Model For Pt Er Exitmentioning

confidence: 99%

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

et al. 2015

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“…Some aberrant soluble proteins in the secretory pathway may escape the ER quality control machinery and are degraded instead in the vacuole (Hong et al, 1996;Holkeri and Makarow, 1998;Jorgensen et al, 1999;Coughlan et al, 2004; reviewed in Arvan et al, 2002). Furthermore, Spear and Ng (2003) reported that the ERAD pathway can be saturated by CPY* overexpression and that excess CPY* is degraded in the vacuole after transiting through the Golgi.…”

Section: Introductionmentioning

confidence: 99%

Characterization of anERADGene asVPS30/ATG6Reveals Two Alternative and Functionally Distinct Protein Quality Control Pathways: One for Soluble Z Variant of Human α-1 Proteinase Inhibitor (A1PiZ) and Another for Aggregates of A1PiZ

Kruse

Brodsky

McCracken

2006

MBoC

189

185

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The Z variant of human ␣-1 proteinase inhibitor (A1PiZ) is a substrate for endoplasmic reticulum-associated protein degradation (ERAD). To identify genes required for the degradation of this protein, A1PiZ degradation-deficient (add) yeast mutants were isolated. The defect in one of these mutants, add3, was complemented by VPS30/ATG6, a gene that encodes a component of two phosphatidylinositol 3-kinase (PtdIns 3-kinase) complexes: complex I is required for autophagy, whereas complex II is required for the carboxypeptidase Y (CPY)-to-vacuole pathway. We found that upon overexpression of A1PiZ, both PtdIns 3-kinase complexes were required for delivery of the excess A1PiZ to the vacuole. When the CPY-to-vacuole pathway was compromised, A1PiZ was secreted; however, disruption of autophagy led to an increase in aggregated A1PiZ rather than secretion. These results suggest that excess soluble A1PiZ transits the secretion pathway to the trans-Golgi network and is selectively targeted to the vacuole via the CPY-to-vacuole sorting pathway, but excess A1PiZ that forms aggregates in the endoplasmic reticulum is targeted to the vacuole via autophagy. These findings illustrate the complex nature of protein quality control in the secretion pathway and reveal multiple sites that recognize and sort both soluble and aggregated forms of aberrant or misfolded proteins. INTRODUCTIONCell function and survival depend on protein quality control to identify and remove aberrant proteins. Although two cellular sites of proteolysis are known, the lysosome/vacuole and cytoplasmic 26S proteasome, the recognition of aberrant proteins and mechanisms for delivery to these sites are still being defined. Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control process in which aberrant or misassembled proteins in the secretory pathway are identified and removed (reviewed in Hampton, 2002;Tsai et al., 2002;Kostova and Wolf, 2003;McCracken and Brodsky, 2003). After entering the endoplasmic reticulum (ER), a nascent protein that fails to fold or assemble properly can be "recognized" by the ER quality control machinery, retained within the ER, and then retrotranslocated to the cytoplasm where it is degraded by the proteasome.The recognition of ERAD substrates must exhibit flexibility to distinguish slowly folding proteins from aberrant proteins. Molecular chaperones play a critical role in this selection process; for example, the ER heat-shock protein (Hsp70), BiP, is vital for the selection of soluble substrates and is believed to hold the substrates in an unfolded state competent for retrotranslocation (Nishikawa et al., 2001;Kabani et al., 2003).The complexity of the ERAD pathway has emerged with the identification of new ERAD substrates and the components required for their selection and degradation in yeast. For example, the analysis of topologically distinct ERAD substrates indicates that molecular chaperones in the cytoplasm and in the ER lumen distinguish membrane and soluble substrates, respectively (Huyer et al., 20...

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“…Moreover, immunocytochemistry showed that both forms of AgRP were distributed in AtT20D16V cells in a similar fashion. Neither form of AgRP was found in the ER or in lysosomes, which would be indicative of the formation of a misfolded protein [23]. Both Ala67 and Thr67 AgRP accumulated in the Golgi apparatus, from which the proteins were probably directed into the regulated secretory pathway.…”

Section: Discussionmentioning

confidence: 95%

“…These cells contain a regulated secretory pathway and as such are a good model system for the synthesis, sorting and trafficking of AgRP in neurons. Misfolding of proteins may lead to accumulation in the endoplasmic reticulum (ER) or to delivery of these proteins to lysosomes for degradation (reviewed in [23] Therefore, co-localisation of both AgRP proteins with the ER, Golgi apparatus and lysosomes was analysed.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness

Rijke

Jackson

Garner

et al. 2005

Biochemical Pharmacology

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AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the nonconservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions. #

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Secretory Pathway Quality Control Operating in Golgi, Plasmalemmal, and Endosomal Systems

Cited by 183 publications

References 97 publications

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

Characterization of anERADGene asVPS30/ATG6Reveals Two Alternative and Functionally Distinct Protein Quality Control Pathways: One for Soluble Z Variant of Human α-1 Proteinase Inhibitor (A1PiZ) and Another for Aggregates of A1PiZ

Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness

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