FK-binding protein is associated with the ryanodine receptor of skeletal muscle in vertebrate animals.
The ryanodine receptor/calcium release channel (RyR1) of sarcoplasmic reticulum from rabbit skeletal muscle terminal cisternae (TC) contains four tightly associated FK506-binding proteins (FKBP12). Dissociation and reconstitution studies have shown that RyR1 can be modulated by FKBP12, which helps to maintain the channel in the quiescent state. In this study, we found that the association of FKBP with RyR1 of skeletal muscle is common to each of the five classes of vertebrates. TC from skeletal muscle representing animals from different vertebrates, i.e. mammals (rabbit), birds (chicken), reptiles (turtle), fish (salmon and rainbow trout), and amphibians (frog), were isolated. For each, we find the following: 1) FKBP12 is localized to the TC (there are four FKBP binding sites/ryanodine receptor); 2) soluble FKBP exchanges with the bound form on RyR1 of TC; 3) release of FKBP from terminal cisternae by drug (FK590) treatment leads to a significant reduction in the net calcium loading rate, consistent with channel activation (the calcium loading rate is restored to the control value by reconstitution with FKBP12); and 4) RyR1 of skeletal muscle TC can bind to and exchange with either FKBP12 or FKBP12.6 (FKBP12.6 is the novel FKBP isoform found selectively associated with RyR2 of dog cardiac sarcoplasmic reticulum). We conclude that FKBP is an integral part of the RyR1 of skeletal muscle in each of the classes of vertebrate animals. The studies are consistent with a role for FKBP in skeletal muscle excitation-contraction coupling.
Qi
Y
Y
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Ogunbunmi
E M
EM
Freund
E A
EA
Timerman
A P
AP
Fleischer
S
S
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D020104:Immunophilins / Q000302:isolation & purification / Q000378:metabolism*; D009124:Muscle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000302:isolation & purification / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins; D014714:Vertebrates / Q000378:metabolism*
D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D002118:Calcium