Specific interaction of FK506 binding protein (FKBP) isoforms with the ryanodine/CaィイD12+ィエD1 release channel subtypes

钙释放通道（CRC）/骨骼（Sk）和（C）肌肉糖复合体视网膜（SR）的瑞诺丁受体是具有结构形态的异分子复合体。（ryanodine receptor（RYR）1 receptor）伊D24伊D2 （FKBP 12）伊D24伊D2 and（RYP2 protomer）伊D24伊D2 （FKBP 12. 6）伊D24伊D2， respectively， where FKBP 12 and FKBP 12. 6 are isoforms of the 12-kDa receptor for the immunosuppressant drug FK506。使用D135 D1 S-labeled FKBP 12和D135 FKBP12.6作为研究与CRC的交互的探针，我们找到： 1）模拟其操作在skeletal muscle sarcoplasmic reticulum （SkMSR），FK 506 dissociates FKBP12.6 from CSR ; 2） both FKBP isoforms绑定到FKBP-stripped SkMSR并与endogenously bound FKBP 12 of SkMSR的交换;和3）通过对比，只有FKBP 12.6与内定绑定的FKBP 12.6进行更改或重新绑定到FKBP-删除CSR。这种选择性的绑定似乎解释了为什么心脏CRC与FKBP 12.6分离为复合体，而骨骼肌肉CRC与FKBP 12.6分离为复合体，也就是说，骨骼肌肉CRC与FKBP 12分离为复合体中的两种肌肉类型。在与FKBP从骨骼肌肉移除的FKBP频道的活动形成对比时，在FKBP-剥离CSR中没有检测到CRC活动。This deferential action of FKBP may reflect a fundamental difference in the modulation of excitation-contraction coupling in heart versus skeletal muscle. we也曾研究过FKBP is associated with the RYR in situ by immunolocaliation studies。在大鼠骨骼肌肉部分，RYR和FKBP都被检测到具有整个肌肉长度的横向带。当相同的部分被双重证明与反RYR和反FKBP抗体，FKBP的乐队在RYR的乐队上超级植入。这些结果建议FKBP与RYR在原位和调节RYR/CRC在骨骼肌肉中的功能。

The calcium release channels (CRC)/ryanodine receptor of skeletal (Sk) and (C) muscle sarcoplasmic reticulum (SR) are hetero-oligomeric complexes with the structural formulas (ryanodine receptor(RYR)1 receptor)ィイD24ィエD2 (FKBP12)ィイD24ィエD2 and (RYP2 protomer)ィイD24ィエD2 (FKBP12.6)ィイD24ィエD2, respectively, where FKBP12 and FKBP12.6 are isoforms of the 12-kDa receptor for the immunosuppressant drug FK506. Using ィイD135ィエD1S-labeled FKBP12 and ィイD135ィエD1S-labeled FKBP12.6 as probes to study the interaction with CRC, we find that : 1) analogous to its action in skeletal muscle sarcoplasmic reticulum (SkMSR), FK506 dissociates FKBP12.6 from CSR ; 2) both FKBP isoforms bind to FKBP-stripped SkMSR and exchange with endogenously bound FKBP12 of SkMSR ; and 3) by contrast, only FKBP12.6 exchanges with endogenously bound FKBP12.6 or rebinds to FKBP-stripped CSR. This selective binding appears to explain why the cardiac CRC is isolated as a complex with FKBP12.6, whereas the skeletal muscle CRC is isolated as a complex with FKBP12.6 although only FKBP12 is detectable in the myoplasm of both muscle types. In contrast to the activation of the channel by removal of FKBP from skeletal muscle, no activation is detected in CRC activity in FKBP-stripped CSR. This deferential action of FKBP may reflect a fundamental difference in the modulation of excitation-contraction coupling in heart versus skeletal muscle.we also examined whether FKBP is associated with the RYR in situ by immunolocalization studies. In rat skeletal muscle section, both the RYR and FKBP were detected as transverse bands with periodicity along the full length of the muscle fiber. When the same section was dual-proved with anti-RYR and anti-FKBP antibody, the bands of FKBP superimposed upon the bands of the RYR. These results suggest that FKBP is associated with the RYR in situ and modulates the function of the RYR/CRC in skeletal muscle.