FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels

FEBS Letters

Mackrill, John J.²  O'Neill, Cora²  Sorrentino, Vincenzo¹  Carmody, Mark² 

[1] Molecular Medicine Section, Department of Neuroscience, University of Siena, 53100 Siena, Italy;Department of Biochemistry, University College Cork, Lee Maltings, Cork, Ireland

关键词: FKBP12;    Ryanodine receptor;    Inositol 1;    4;    5-trisphosphate receptor;    Calcineurin;    Intracellular Ca2+ release channel;    FK506;    Skeletal muscle;    Brain;    Cardiac muscle;    CHAPS;    3-((cholamidopropyl)dimethylammonio)-1-propane-sulfonate;    FKBP12;    FK506 binding protein;    12 kDa;    FKBP12.6;    FK506 binding protein;    12.6 kDa;    FKWB;    FKBP wash buffer;    GST;    glutathione-S-transferase;    IP3R;    inositol 1;    4;    5-trisphosphate receptor;    PMSF;    phenylmethyl-sulfonylfluoride;    RyR;    ryanodine receptor;    SR;    sarcoplasmic reticulum;   

DOI  :  10.1016/S0014-5793(01)02787-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

This study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP₃R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12–glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP₃R isoforms and calcineurin.

【 授权许可】

Unknown