Differential phosphorylation of calreticulin affects AT1 receptor mRNA stability in VSMC

Mueller, Cornelius F.H.; Wassmann, Kerstin; Berger, Anja; Holz, S; Waßmann, Sven; Nickenig, Georg

doi:10.1016/j.bbrc.2008.04.011

Cited by 17 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the arginylation machinery is located in the cytosol, the discovery of arginylated CRT lacking its signal peptide is a good evidence of its alternative cytosolic localization. Cytosolic CRT may participate in many functions, such as regulation of nuclear hormone receptors localization [45] and mRNA stability [46]. CRT KO in mice is embryonically lethal at E14.5 as a consequence of an impaired cardiac development [47].…”

Section: The Lectins (Cnx and Crt)mentioning

confidence: 99%

A sweet code for glycoprotein folding

2015

View full text Add to dashboard Cite

a b s t r a c tGlycoprotein synthesis is initiated in the endoplasmic reticulum (ER) lumen upon transfer of a glycan (Glc 3 Man 9 GlcNAc 2 ) from a lipid derivative to Asn residues (N-glycosylation). N-Glycan-dependent quality control of glycoprotein folding in the ER prevents exit to Golgi of folding intermediates, irreparably misfolded glycoproteins and incompletely assembled multimeric complexes. It also enhances folding efficiency by preventing aggregation and facilitating formation of proper disulfide bonds. The control mechanism essentially involves four components, resident lectin-chaperones (calnexin and calreticulin) that recognize monoglucosylated polymannose protein-linked glycans, lectin-associated oxidoreductase acting on monoglucosylated glycoproteins (ERp57), a glucosyltransferase that creates monoglucosylated epitopes in protein-linked glycans (UGGT) and a glucosidase (GII) that removes the glucose units added by UGGT. This last enzyme is the only mechanism component sensing glycoprotein conformations as it creates monoglucosylated glycans exclusively in not properly folded glycoproteins or in not completely assembled multimeric glycoprotein complexes. Glycoproteins that fail to properly fold are eventually driven to proteasomal degradation in the cytosol following the ER-associated degradation pathway, in which the extent of N-glycan demannosylation by ER mannosidases play a relevant role in the identification of irreparably misfolded glycoproteins.

show abstract

Section: The Lectins (Cnx and Crt)mentioning

confidence: 99%

A sweet code for glycoprotein folding

2015

View full text Add to dashboard Cite

show abstract

“…A good argument in favor of cytosolic/nuclear CRT is the detection of postranslational modifications exclusively occurring on those sites. For instance, CRT has been found to be phosphorylated by src kinase [25] and PKC [26], [27], it also can be modified in Ser/Thr with O-GlcNAc [28] and arginylated CRT has been found in cytosolic stress granules [29].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Calcium Regulates the Retrotranslocation of Trypanosoma Cruzi Calreticulin to the Cytosol

et al. 2010

View full text Add to dashboard Cite

For most secretory pathway proteins, crossing the endoplasmic reticulum (ER) membrane is an irreversible process. However, in some cases this flow can be reversed. For instance, misfolded proteins retained in the ER are retrotranslocated to the cytosol to be degraded by the proteasome. This mechanism, known as ER associated degradation (ERAD), is exploited by several bacterial toxins to gain access to the cytosol. Interestingly, some ER resident proteins can also be detected in the cytosol or nucleus, calreticulin (CRT) being the most studied. Here we show that in Trypanosoma cruzi a minor fraction of CRT localized to the cytosol. ER calcium depletion, but not increasing cytosolic calcium, triggered the retrotranslocation of CRT in a relatively short period of time. Cytosolic CRT was subsequently degraded by the proteasome. Interestingly, the single disulfide bridge of CRT is reduced when the protein is located in the cytosol. The effect exerted by ER calcium was strictly dependent on the C-terminal domain (CRT-C), since a CRT lacking it was totally retained in the ER, whereas the localization of an unrelated protein fused to CRT-C mirrored that of endogenous CRT. This finding expands the regulatory mechanisms of protein sorting and may represent a new crossroad between diverse physiological processes.

show abstract

“…27 and Fig. 3 A , line 5), an effect associated with the profibrotic processes in the literature (28). Another result showed that glomerular calreticulin protein expression was observed to be unmodified in a mouse model of diabetic nephropathy (ref.…”

Section: Resultsmentioning

confidence: 78%

The KUPKB: a novel Web application to access multiomics data on kidney disease

et al. 2012

View full text Add to dashboard Cite

The information gathered from the large number of omics experiments in renal biology is underexplored, as it is scattered over many publications or held in supplemental data. To address this, we have developed an open-source Kidney and Urinary Pathway Knowledge Base (KUPKB) that facilitates simple exploration of these omics data. The KUPKB currently comprises 220 data sets (miRNA, mRNA, proteins, and metabolites) extracted from existing publications or databases. Researchers can explore the integrated data using the iKUP browser, and a simple template is provided to submit new omics data sets to the knowledge base. As an example of iKUP's use, we show how we identified, in silico, calreticulin as a protein induced in human interstitial fibrosis and tubular atrophy (IFTA) in chronic kidney transplant rejection; a link that would have been difficult to establish using existing Web-based tools. Using immunohistochemistry, we validated in vivo this in silico result in human and rat biopsies of IFTA, thus identifying calreticulin as a potential new player in chronic kidney transplant rejection. The KUPKB provides a simple tool that enables users to quickly survey a wide range of omics data sets and has been shown to facilitate rapid hypothesis generation in the context of renal pathophysiology.

show abstract

Differential phosphorylation of calreticulin affects AT1 receptor mRNA stability in VSMC

Cited by 17 publications

References 19 publications

A sweet code for glycoprotein folding

A sweet code for glycoprotein folding

Endoplasmic Reticulum Calcium Regulates the Retrotranslocation of Trypanosoma Cruzi Calreticulin to the Cytosol

The KUPKB: a novel Web application to access multiomics data on kidney disease

Contact Info

Product

Resources

About