Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation.
Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin. We have investigated the possibility that calsequestrin is a luminal calcium concentration sensor for the ryanodine receptor. We measured the luminal calcium concentration at which calsequestrin dissociates from the ryanodine receptor and the effect of calsequestrin on the response of the ryanodine receptor to changes in luminal calcium. We provide electrophysiological and biochemical evidence that: 1), luminal calcium concentration of >/=4 mM dissociates calsequestrin from junctional face membrane, whereas in the range of 1-3 mM calsequestrin remains attached; 2), the association with calsequestrin inhibits ryanodine receptor activity, but amplifies its response to changes in luminal calcium concentration; and 3), under physiological calcium conditions (1 mM), phosphorylation of calsequestrin does not alter its ability to inhibit native ryanodine receptor activity when the anchoring proteins triadin and junctin are present. These data suggest that the quaternary complex is intact in vivo, and provides further evidence that calsequestrin is involved in the sarcoplasmic reticulum calcium signaling pathway and has a role as a luminal calcium sensor for the ryanodine receptor.
Beard
Nicole A
NA
John Curtin School of Medical Research, Australian Capital Territory, Australia. nicole.beard@anu.edu.au
Casarotto
Marco G
MG
Wei
Lan
L
Varsányi
Magdolna
M
Laver
Derek R
DR
Dulhunty
Angela F
AF
D000135:Acid Phosphatase / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002155:Calsequestrin / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D047390:Casein Kinase II / Q000737:chemistry; D002845:Chromatography; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D005978:Glutathione / Q000378:metabolism; D015151:Immunoblotting; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000737:chemistry; D009124:Muscle Proteins / Q000737:chemistry; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis* / Q000737:chemistry; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D002352:Carrier Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C498269:TRDN protein, human; C070048:triadin; C498842:Junctin protein, Oryctolagus cuniculus; D006899:Mixed Function Oxygenases; D047390:Casein Kinase II; D000135:Acid Phosphatase; D005978:Glutathione; D002118:Calcium
J Biol Chem. 1974 Sep 25;249(18):5867-71
4472093
J Membr Biol. 1995 Sep;147(1):7-22
8531200
J Membr Biol. 1980 Oct 31;56(3):241-8
6779012
FEBS Lett. 1980 Dec 29;122(2):227-30
6258979
Biochim Biophys Acta. 1983 Jul 13;732(1):99-109
6307368
J Biol Chem. 1983 Aug 25;258(16):9662-8
6309780
FEBS Lett. 2000 Apr 21;472(1):73-7
10781808
J Biol Chem. 2000 Jun 9;275(23):17639-46
10748065
Biochemistry. 2000 Jul 4;39(26):7807-12
10869186
Circ Res. 2000 Aug 4;87(3):201-6
10926870
FEBS Lett. 2000 Dec 8;486(2):178-82
11113462
J Physiol. 2001 Mar 15;531(Pt 3):715-28
11251053
Biophys J. 2002 Jan;82(1 Pt 1):310-20
11751318
Front Biosci. 2002 Jun 1;7:d1454-63
12045014
J Biol Chem. 2002 Oct 4;277(40):37154-60
12147690
Biophys J. 2002 Nov;83(5):2491-501
12414683
J Biol Chem. 2003 May 2;278(18):16176-82
12594204
Biophys J. 2004 Feb;86(2):797-804
14747315
J Biol Chem. 1995 Dec 22;270(51):30787-96
8530521
Pflugers Arch. 1996 May;432(1):155-7
8662280
Biochim Biophys Acta. 1996 Aug 14;1283(1):89-100
8765099
Biophys J. 1996 Jun;70(6):2600-15
8744299
J Physiol. 1996 Jun 1;493 ( Pt 2):357-70
8782101
J Biol Chem. 1997 Sep 12;272(37):23389-97
9287354
Nat Struct Biol. 1998 Jun;5(6):476-83
9628486
Biophys J. 2004 Apr;86(4):2121-8
15041652
Biophys J. 1998 Dec;75(6):2801-10
9826602
Biochem J. 1999 Jan 1;337 ( Pt 1):19-22
9854019
J Biol Chem. 1999 Apr 30;274(18):12278-83
10212196
FEBS Lett. 1999 Jul 9;454(3):240-6
10431815
J Biol Chem. 1974 Apr 25;249(8):2357-65
4856651
Prog Biophys Mol Biol. 2004 May;85(1):33-69
15050380
Cell Calcium. 2004 Jun;35(6):621-8
15110152
Nature. 1970 Aug 15;227(5259):680-5
5432063
J Biol Chem. 1972 Dec 10;247(23):7835-7
4264137
J Cell Biol. 1973 Jan;56(1):120-8
4118450
J Biol Chem. 1983 Oct 10;258(19):11932-6
6619149
J Biol Chem. 1984 May 25;259(10):6248-52
6725251
J Cell Biol. 1984 Sep;99(3):875-85
6147356
Biochemistry. 1986 Jan 14;25(1):244-51
3754148
J Cell Biol. 1986 Sep;103(3):741-53
2943746
J Cell Biol. 1987 Jul;105(1):49-56
3497158
J Biol Chem. 1988 Jan 25;263(3):1376-81
3335548
Science. 1988 Oct 7;242(4875):99-102
2459777
Biochemistry. 1989 Aug 8;28(16):6764-71
2790030
Biophys J. 1990 Mar;57(3):471-5
2306496
J Membr Biol. 1990 Feb;113(3):237-51
2159517
J Biol Chem. 1991 Jan 5;266(1):391-8
1985907
Biochemistry. 1990 Oct 2;29(39):9281-9
2176846
Biotechnology. 1992;24:145-9
1422008
J Biol Chem. 1993 Nov 25;268(33):24635-41
8227022
Biochem Biophys Res Commun. 1994 Jan 14;198(1):144-9
8292016
FEBS Lett. 1994 Oct 3;352(3):369-74
7523191
J Biol Chem. 1994 Nov 11;269(45):28359-65
7961775
Mol Cell Biochem. 1994 Jun 15;135(1):61-70
7816057
Biophys J. 1995 Feb;68(2):507-15
7696504
J Biol Chem. 1995 Apr 21;270(16):9027-30
7721813
Biophys J. 1995 Jul;69(1):106-19
7669888
J Membr Biol. 1995 Jul;146(2):133-44
7473684
FEBS Lett. 1979 Jul 1;103(1):85-8
467659