TY - JOUR
T1 - Altered calcium pump and secondary deficiency of γ-sarcoglycan and microspan in sarcoplasmic reticulum membranes isolated from δ-sarcoglycan knockout mice
AU - Solares-Pérez, Alhondra
AU - Álvarez, Rocío
AU - Crosbie, Rachelle H.
AU - Vega-Moreno, Jesús
AU - Medina-Monares, Joel
AU - Estrada, Francisco J.
AU - Ortega, Alicia
AU - Coral-Vazquez, Ramón
N1 - Funding Information:
R.M.C.V. was supported by grants from the Instituto Mexicano del Seguro Social (IMSS) (grant 2006/1A/I/078) and Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant #55199). A.O. was supported by grant #DGAPA-IN227106 and IN227809 from Dirección General del Personal Académico, Universidad Nacional Autónoma de México, and Consejo Nacional de Ciencia y Tecnología (CONACyT) grant #24792. A.S.P. was supported during the Ph.D. program (Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México) by scholarships from Consejo Nacional de Ciencia y Tecnología, México (#223377), IMSS and Dirección General de Estudios de Postgrado, Instituto de Investigaciones Biomédicas, UNAM.
PY - 2010/7
Y1 - 2010/7
N2 - 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 δ-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 δ-SG isoforms in TT and SR results in a secondary deficiency of γ-SG and μSPN. 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 δ-SG isoforms may stabilize the expression of γ-SG and μSPN 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.
AB - 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 δ-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 δ-SG isoforms in TT and SR results in a secondary deficiency of γ-SG and μSPN. 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 δ-SG isoforms may stabilize the expression of γ-SG and μSPN 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.
KW - Calcium
KW - Knockout
KW - Microspan
KW - Muscular dystrophy
KW - Pathology
KW - SERCA1
KW - Sarcoglycans
KW - Sarcoplasmic reticulum
KW - Skeletal muscle
KW - δ-Sarcoglycan
UR - http://www.scopus.com/inward/record.url?scp=77956010257&partnerID=8YFLogxK
U2 - 10.1016/j.ceca.2010.06.003
DO - 10.1016/j.ceca.2010.06.003
M3 - Artículo
C2 - 20638123
SN - 0143-4160
VL - 48
SP - 28
EP - 36
JO - Cell Calcium
JF - Cell Calcium
IS - 1
ER -