High impact information on Canx

• Autocrine motility factor receptor (AMF-R) is a marker for a smooth subdomain of the ER, shown here by confocal microscopy to be distinct from, yet closely associated with the calnexin- or calreticulin-labeled ER [1].
• This is deduced from the effect of antibodies to the COOH-terminal tail of alpha(2)p24, but not of antibodies to the COOH-terminal tail of calnexin on this reconstitution, as well as the demonstrated recruitment of COPI coatomer to VTCs, its augmentation by GTPgammaS, inhibition by Brefeldin A (BFA), or depletion of beta-COP from cytosol [2].
• Taken together with studies revealing calnexin association with CK2 and ERK-1, a model is proposed whereby phosphorylation of calnexin leads to a potential increase in glycoprotein folding close to the translocon [3].
• Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes [3].
• Remarkably, DLP1-positive structures coalign with microtubules and, most strikingly, with endoplasmic reticulum tubules as verified by double labeling with antibodies to calnexin and Rab1 as well as by immunoelectron microscopy [4].

Biological context of Canx

• Partial amino acid sequence analysis revealed that p93 was close to 100% homologous with a recently identified ER Ca(2+)-binding protein known as calnexin [5].
• Using truncated RNA templates we found that calnexin did not associate with the first four TM domains but retained affinity for the construct encoding TM domains 5 and 6, which contains the glycosylation sites [6].
• Stable transfection of FR3T3 rat fibroblast cells with p79 cDNA analysed by electron microscopy following immunolabelling of ultra-thin cryosections revealed a localization of p79 in the secretory pathway, mainly in the endoplasmic reticulum and the Golgi region, where it is specifically associated with the molecular chaperone calnexin [7].

Anatomical context of Canx

• We propose that ERp57 acts in concert with calnexin and calreticulin to modulate glycoprotein folding and enforce the glycoprotein specific quality control mechanism operating in the endoplasmic reticulum [8].
• This, together with the citrate data, strongly suggests that p93/calnexin, in isolated nuclear envelopes, is mostly bound to the inner membrane [5].
• Calnexin (but not calreticulin) associated with newly synthesized FLAG (DYKDDDDK epitope)-tagged type-III IP(3)R expressed in COS-7 cells [6].
• By Western blot analysis, all fractions contained calnexin, p58, sarcoplasmic reticulum type Ca(2+)-ATPase, and IP3 receptor [9].
• Immunoblot experiments revealed that raft-like membranes prepared by detergent extraction or sonication were free of Golgi apparatus or endoplasmic reticulum protein markers (beta-COP and calnexin, respectively) and that they were not substantially contaminated by transferrin receptor (a non-raft protein) [10].

Associations of Canx with chemical compounds

• A subset of these luminal components are specific for glycoproteins, and, like calnexin and calreticulin, the thiol-dependent reductase ERp57 has been shown to interact specifically with soluble secretory proteins bearing N-linked carbohydrate [8].
• Biosynthesis of inositol trisphosphate receptors: selective association with the molecular chaperone calnexin [6].
• Glucose trimming from newly synthesized glycoproteins regulates their interaction with the calnexin/calreticulin chaperone system [11].
• The interaction of calnexin with newly synthesized type-I IP(3)R was transient and inhibited by treatment of the cells with dithiothreitol or the glucosidase inhibitor N-methyldeoxynojirimicin [6].

Other interactions of Canx

• This enzyme catalyzes the formation of disulfide bonds in CNX and CRT-bound glycoprotein substrates [12].
• PDI was clearly enriched in the light density fraction while calnexin was broadly distributed [13].
• These peripheral smooth ER elements also reacted at the immunofluorescence level for ER marker 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as for calnexin and protein disulfide isomerase [14].
• Addition of glucosidase inhibitors prevented the association of calnexin with in vitro translated type-I TM construct [6].
• The distribution of endoplasmic reticulum (ER) markers (RNA, signal-sequence receptor alpha, calnexin, calreticulin, the immunoglobulin-binding protein Bip) and markers of intracellular rapidly exchanging Ca2+ stores [Ca2+ channels sensitive to either Ins(1,4,5)P3 or ryanodine) was investigated biochemically and immunologically [15].

References