Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12

被引:41
作者
Dargan, SL [1 ]
Lea, EJA [1 ]
Dawson, AP [1 ]
机构
[1] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
关键词
calcium; immunophilin; InsP(3)R; ryanodine receptor;
D O I
10.1042/0264-6021:3610401
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
FK506-binding protein (FKBP12) is highly expressed in neuronal tissue, where it is proposed to localize calcineurin to intracellular calcium-release channels, ryanodine receptors and Ins(1,4,5)P, receptors (InsP(3)Rs). The effects of FKBP12 on ryanodine receptors have been well characterized but the nature and function of binding of FKBP12 to InsP(3)R is more controversial, with evidence for and against a tight interaction between these two proteins. To investigate this, we incorporated purified type-l InsP.,R from rat cerebellum into planar lipid bilayers to monitor the effects of exogenous recombinant FKBP12 on single-channel activity, using K+ as the current carrier. Here we report for the first time that FKBP12 causes a substantial change in single-channel properties of the type-1 InsP(3)R, specifically to increase the amount of time the channel spends in a fully open state. In the presence of ATP, FKBP12 can also induce co-ordinated gating with neighbouring receptors. The effects of FKBP 12 were reversed by FK506. We also present data showing that rapamycin, at sub-optimal concentrations of Ins(2,4,S)P-3, decreases the rate of calcium release from cerebellar microsomes. These results provide evidence for a direct functional interaction between FKBP12 and the type-1 InsP(3)R.
引用
收藏
页码:401 / 407
页数:7
相关论文
共 30 条
  • [1] Calcineurin regulates ryanodine receptor/Ca2+-release channels in rat heart
    Bandyopadhyay, A
    Shin, DW
    Ahn, JO
    Kim, DH
    [J]. BIOCHEMICAL JOURNAL, 2000, 352 : 61 - 70
  • [2] Calcium - a life and death signal
    Berridge, MJ
    Bootman, MD
    Lipp, P
    [J]. NATURE, 1998, 395 (6703) : 645 - 648
  • [3] Elementary and global aspects of calcium signalling
    Berridge, MJ
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1997, 499 (02): : 291 - 306
  • [4] Muscle contraction - Coordinated feet and the dance of ryanodine receptors
    Bers, DM
    Fill, M
    [J]. SCIENCE, 1998, 281 (5378) : 790 - 791
  • [5] ATP MODULATES THE FUNCTION OF INOSITOL 1,4,5-TRISPHOSPHATE-GATED CHANNELS AT 2 SITES
    BEZPROZVANNY, I
    EHRLICH, BE
    [J]. NEURON, 1993, 10 (06) : 1175 - 1184
  • [6] STABILIZATION OF CALCIUM-RELEASE CHANNEL (RYANODINE RECEPTOR) FUNCTION BY FK506-BINDING PROTEIN
    BRILLANTES, AMB
    ONDRIAS, K
    SCOTT, A
    KOBRINSKY, E
    ONDRIASOVA, E
    MOSCHELLA, MC
    JAYARAMAN, T
    LANDERS, M
    EHRLICH, BE
    MARKS, AR
    [J]. CELL, 1994, 77 (04) : 513 - 523
  • [7] A MAMMALIAN PROTEIN TARGETED BY G1-ARRESTING RAPAMYCIN-RECEPTOR COMPLEX
    BROWN, EJ
    ALBERS, MW
    SHIN, TB
    ICHIKAWA, K
    KEITH, CT
    LANE, WS
    SCHREIBER, SL
    [J]. NATURE, 1994, 369 (6483) : 756 - 758
  • [8] Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms
    Bultynck, G
    De Smet, P
    Weidema, AF
    Heyen, MV
    Maes, K
    Callewaert, G
    Missiaen, L
    Parys, JB
    De Smedt, H
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2000, 525 (03): : 681 - 693
  • [9] Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor
    Bultynck, G
    De Smet, P
    Rossi, D
    Callewaert, G
    Missiaen, L
    Sorrentino, V
    De Smedt, H
    Parys, JB
    [J]. BIOCHEMICAL JOURNAL, 2001, 354 : 413 - 422
  • [10] FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400-1401) and anchors calcineurin to this FK506-like domain
    Cameron, AM
    Nucifora, FC
    Fung, ET
    Livingston, DJ
    Aldape, RA
    Ross, CA
    Snyder, SH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) : 27582 - 27588