title: Altered calcium pump and secondary deficiency of gamma-sarcoglycan and microspan in sarcoplasmic reticulum membranes isolated from delta-sarcoglycan knockout mice.
abstract: Sarcoglycans (SGs) and sarcospan (SSPN) are transmembrane proteins of the dystrophin-glycoprotein complex. Mutations in the genes encoding SGs cause many inherited forms of muscular dystrophy. In this study, using purified membranes of wild-type (WT) and delta-SG knockout (KO) mice, we found the specific localization of the SG-SSPN isoforms in transverse tubules (TT) and sarcoplasmic reticulum (SR) membranes. Immunoblotting revealed that the absence of delta-SG isoforms in TT and SR results in a secondary deficiency of gamma-SG and microSPN. Our results showed augmented ATP hydrolytic activity, ATP-dependent calcium uptake and passive calcium efflux, probably through SERCA1 in KO compared to WT mice. Furthermore, we found a conformational change in SERCA1 isolated from KO muscle as demonstrated by calorimetric analysis. Following these alterations with mechanical properties, we found an increase in force in KO muscle with the same rate of fatigue but with a decreased fatigue recovery compared to WT. Together our observations suggest, for the first time, that the delta-SG isoforms may stabilize the expression of gamma-SG and microSPN in the TT and SR membranes and that this possible complex may play a role in the maintenance of a stable level of resting cytosolic calcium concentration in skeletal muscle.
authors.affiliation: Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF., México.
authors.forename: Alhondra
authors.initials: A
authors.lastname: Solares-Pérez
authors.forename: Rocío
authors.initials: R
authors.lastname: Alvarez
authors.forename: Rachelle H
authors.initials: RH
authors.lastname: Crosbie
authors.forename: Jesús
authors.initials: J
authors.lastname: Vega-Moreno
authors.forename: Joel
authors.initials: J
authors.lastname: Medina-Monares
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Estrada
authors.forename: Alicia
authors.initials: A
authors.lastname: Ortega
authors.forename: Ramón
authors.initials: R
authors.lastname: Coral-Vazquez
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018763:Muscle Fatigue / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D049031:Sarcoglycans / Q000172:deficiency* / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism
chemical_list: C506944:Atp2a1 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D049031:Sarcoglycans; C491632:Sspn protein, mouse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases