Disease relevance of CASQ2

• This increased activity of the malignant hyperthermia sarcoplasmic reticulum fraction was associated with twofold increased concentration of Ca-ATPase and calsequestrin protein [1].

High impact information on CASQ2

• Collectively, the results provide the first sing of a possible functional interaction between ANKRD1 and CASQ2 and suggest a potentially novel role for both proteins in cardiac Purkinje fibers [2].
• ANKRD1 specifically binds CASQ2 in heart extracts and both proteins are co-enriched in piglet cardiac Purkinje cells [2].
• Reductions in sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin [3].
• Western blot analysis showed that among the smooth muscles studied, the cardiac isoform of calsequestrin is expressed at the highest levels in the stomach [4].
• Calsequestrin was present at lower levels in ileum and trachea, whereas this protein was undetectable in aorta and main pulmonary artery [4].

Biological context of CASQ2

• This difference in amount of Ca++ preload is not explained by results obtained comparing rates of Ca++ uptake, number of ryanodine binding sites or the amounts of calsequestrin among SR vesicles from MH and normal muscle [5].
• Northern blot analysis of hibernating myocardium demonstrated regional downregulation in mRNAs for sarcoplasmic reticulum (SR) proteins phospholamban (0.76 +/- 0.08 vs. 1.07 +/- 0.06, P < 0.02) and SR Ca(2+)-ATPase (0.83 +/- 0.06 vs. 1.02 +/- 0.06, P < 0.05) with no change in calsequestrin (1.08 +/- 0.06 vs. 0.96 +/- 0.05, P = not significant) [6].

Anatomical context of CASQ2

• Specific protein-protein interactions of calsequestrin with junctional sarcoplasmic reticulum of skeletal muscle [7].
• Boars heterozygous for mutated sRyR had lower CS in the hippocampus, which was accompanied by the expression of mRNA for sRyR [8].
• Immunoreactive CS was not detectable in the pituitary gland while low levels were observed in the hypothalamus and frontal cortex [8].
• Earlier, we cloned a 64-kd protein that was identified as calsequestrin, a calcium-binding protein localized in the sarcoplasmic reticulum of striated muscle and extensively studied another cloned 64-kd protein, called 1D, which is expressed in thyroid and eye muscle, and some other tissues [9].
• Calsequestrin, thought to store and release calcium from membrane bound intracellular storage sites is found only in the cytoplasm of outer hair cells [10].

Associations of CASQ2 with chemical compounds

• Whereas calsequestrin from pig presented the same apparent M(r) in sodium dodecyl sulphate polyacrylamide gels as the well characterized protein from rabbit, the apparent M(r) of both sarcalumenin and HCP was lower in pig than in rabbit [4].
• Minor protein components of triads and of sarcoplasmic reticulum (SR) terminal cisternae (TC), i.e. 47 and 37 kDa peptides and 31-30 kDa and 26-25 kDa peptide doublets, were identified from their ability to bind 125I calsequestrin (CS) in the presence of EGTA [7].
• Following DEAE-Sephadex ion-exchange chromatography of the HgCl2/ deoxycholate-solubilized material, calsequestrin was obtained in nearly homogeneous form [11].
• Calsequestrin was selectively solubilized from porcine skeletal muscle sarcoplasmic reticulum by incubation with HgCl2 and deoxycholate [11].
• MHS and normal heavy SR preparations isolated from the vastus intermedius muscle had similar yields, polyacrylamide gel electrophoretic patterns, Ca2(+)-ATPase activities, mitochondrial enzyme activities, calsequestrin contents, and maximal [3H]ryanodine-binding activities [12].

Analytical, diagnostic and therapeutic context of CASQ2

• Nuclear run-on assays showed increased transcription for Ca(2+)-ATPase and calsequestrin at 90 min of reperfusion, supporting the view that increased mRNA levels seen with northern hybridisation were due to increased transcription of the respective gene [13].
• From an analysis of subcellular membranes separated by sucrose gradient centrifugation it is concluded that the protein with Mr 55,000 from the smooth muscle is confined to the endoplasmic reticulum, the same subcellular structure from which, in heart muscle, calsequestrin can be isolated [14].

References