Regulation of Bcl-xl channel activity by calcium.
Recent studies have demonstrated that the anti-apoptotic proteins, Bcl-2 and Bcl-xl, with the carboxyl-terminal hydrophobic domain removed, form cation-selective channels in the lipid bilayer reconstitution system. However, the regulatory properties of these channels are unknown. In this study, we investigated the ion-conducting properties of full-length Bcl-xl in the lipid bilayer reconstitution system. Our findings indicate that Bcl-xl forms a cation-selective channel that conducts sodium but not calcium and that Bcl-xl channel activity is reversibly inhibited by luminal calcium with a half-dissociation constant of approximately 60 microM. This calcium-dependent regulation of the Bcl-xl channel provides new insights into the roles of calcium and Bcl-2-related proteins in the programmed cell death pathway.
Lam
M
M
Department of Pharmacology, Case Western Reserve University, Cleveland,Ohio 44106, USA.
Bhat
M B
MB
Nuñez
G
G
Ma
J
J
Distelhorst
C W
CW
D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D017931:DNA Primers; D007473:Ion Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D002118:Calcium