Displacement of SERCA from SR lipid caveolae-related domains by Bcl-2: a possible mechanism for SERCA inactivation.
Bcl-2 exerts its anti-apoptotic effect in part through the regulation of Ca2+ homeostasis at the level of the endoplasmic reticulum. Earlier, we demonstrated that a truncated form of Bcl-2, Bcl-2delta21, interacts with and destabilizes the skeletal muscle sarco/endoplasmic reticulum Ca-ATPase (SERCA) [Dremina, E. S., Sharov, V. S., Kumar, K., Zaidi, A., Michaelis, E. K., and Schöneich, C. (2004) Biochem. J. 383, 361-370]. Here we show that (i) the transmembrane (TM) domain of Bcl-2 accelerates SERCA inactivation, (ii) both Bcl-2delta21 and full-length Bcl-2 selectively interact with SERCA1, and (iii) the inactivation of SERCA is accompanied by a translocation of SERCA from caveolae-related domains (CRD) of the sarcoplasmic reticulum (SR). In rat skeletal muscle SR, intact SERCA1 was detected only in the CRD fractions of a sucrose density gradient. Co-incubation of SR with either Bcl-2delta21 or full-length Bcl-2 resulted in both the appearance of Bcl-2delta21 or Bcl-2 in the fractions containing SERCA1 and translocation of SERCA1 from CRD fractions; the latter effect correlated with the loss of the Ca-ATPase activity of the protein.
Dremina
Elena S
ES
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Sharov
Victor S
VS
Schöneich
Christian
C
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013997:Time Factors
C506945:Atp2a1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases