Complex Actions of FKBP12 on RyR1 Ion Channel Activity Consistent with Negative Co-Operativity in FKBP12 Binding to the RyR1 Tetramer.

ABSTRACT: The association of the 12 KDa FK506 binding protein (FKBP12) with ryanodine receptor type 1 (RyR1) in skeletal muscle is thought to suppress RyR1 channel opening and contribute to healthy muscle function. The strongest evidence for this role is increased RyR1 channel activity following FKBP12 dissociation. However, the corollary that channel activity will decrease when FKBP12 is added back to FKBP12-depleted RyR1 is not well established, and when reported, the time- and concentration-dependence of inhibition vary over orders of magnitude. Here, we address this problem with an investigation of the molecular mechanisms of the FKBP12 regulation of RyR1. Muscle processing to obtain sarcoplasmic reticulum (SR) vesicle preparations enriched in RyR1 resulted in substantial FKBP12 dissociation fro

SUBMITTER: Richardson SJ 

PROVIDER: S-EPMC11817637 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature