Structural and functional correlates of a mutation in the malignant hyperthermia-susceptible pig ryanodine receptor

Janies R. Mickelson; C. Michael Knudson; Catharine F.H. Kennedy; Ding I. Yang; Lynn A. Litterer; William E. Rempel; Kevin P. Campbell; Charles F. Louis

doi:10.1016/0014-5793(92)80208-X

Structural and functional correlates of a mutation in the malignant hyperthermia-susceptible pig ryanodine receptor

Janies R. Mickelson, C. Michael Knudson, Catharine F.H. Kennedy, Ding I. Yang, Lynn A. Litterer, William E. Rempel, Kevin P. Campbell, Charles F. Louis

Genetics and Genomics

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

The skeletal muscle ryanodine receptor of malignant hyperthermia-susceptible (MHS) pigs contains a mutation at residue 615 that is highly correlated with various abnormalities in the regulation of sarcoplasmic reticulum (SR) Ca²⁺ channel activity. In isolated SR membranes the Arg⁶¹⁵ to Cys⁶¹⁵ ryanodine receptor mutation is now shown to be directly responsible for an altered tryptic peptide map, due to the elimination of the Arg⁶¹⁵ cleavage site. Furthermore, trypsin treatment released 86-99 kDa ryanodine receptor fragments encompassing residue 615 from the SR membranes. We conclude that the 86-99 kDa domain containing residue 615 is near the cytoplasmic surface of the ryanodine receptor and likely near important Ca²⁺ channel regulatory sites.

Original language	English (US)
Pages (from-to)	49-52
Number of pages	4
Journal	FEBS Letters
Volume	301
Issue number	1
DOIs	https://doi.org/10.1016/0014-5793(92)80208-X
State	Published - Apr 13 1992

Bibliographical note

Funding Information:
.I~~k/,trll~l~T~he a/uthco~rs rwrirshc ,tro/ h.uñk : Dr. Clivc Sl;myhtcr 01 the Howard Huphss Mcdicul loslitutc. University or TL’XIS South-wcstcrn Medical Center, Ibr protein-suqucnciii~ cxpcrtisc. This work was supported by pr;lnts rrom 111~M’u scular Dystrophy Association ol’Amcric;i ;II~ the Niltiunill Pork Producers COUIIC~(lIo J.R.M. und C.F.L.). NIH GM 31382 (to C.F.L.). ;mrl by the University or.Minnc-sotil Agricultural Experiment Stiltion (C.F,L. und W.E,R,), K.P.C. is UII Invcstiyutor ol’ The Ho\vurd Hughes Mcdicul Institute.

Keywords

Calcium release channel
Malignant hyperthermia
Mutation
Ryanodine receptor
Sarcoplasmic reticulum

Publisher link

10.1016/0014-5793(92)80208-X

Find It

Find It at U of M Libraries

Cite this

@article{abbc221f564b4012aa2e3939909dd545,

title = "Structural and functional correlates of a mutation in the malignant hyperthermia-susceptible pig ryanodine receptor",

abstract = "The skeletal muscle ryanodine receptor of malignant hyperthermia-susceptible (MHS) pigs contains a mutation at residue 615 that is highly correlated with various abnormalities in the regulation of sarcoplasmic reticulum (SR) Ca2+ channel activity. In isolated SR membranes the Arg615 to Cys615 ryanodine receptor mutation is now shown to be directly responsible for an altered tryptic peptide map, due to the elimination of the Arg615 cleavage site. Furthermore, trypsin treatment released 86-99 kDa ryanodine receptor fragments encompassing residue 615 from the SR membranes. We conclude that the 86-99 kDa domain containing residue 615 is near the cytoplasmic surface of the ryanodine receptor and likely near important Ca2+ channel regulatory sites.",

keywords = "Calcium release channel, Malignant hyperthermia, Mutation, Ryanodine receptor, Sarcoplasmic reticulum",

author = "Mickelson, {Janies R.} and Knudson, {C. Michael} and Kennedy, {Catharine F.H.} and Yang, {Ding I.} and Litterer, {Lynn A.} and Rempel, {William E.} and Campbell, {Kevin P.} and Louis, {Charles F.}",

note = "Funding Information: .I~~k/,trll~l~T~he a/uthco~rs rwrirshc ,tro/ h.u{\~n}k : Dr. Clivc Sl;myhtcr 01 the Howard Huphss Mcdicul loslitutc. University or TL{\textquoteright}XIS South-wcstcrn Medical Center, Ibr protein-suqucnciii~ cxpcrtisc. This work was supported by pr;lnts rrom 111~M{\textquoteright}u scular Dystrophy Association ol{\textquoteright}Amcric;i ;II~ the Niltiunill Pork Producers COUIIC~(lIo J.R.M. und C.F.L.). NIH GM 31382 (to C.F.L.). ;mrl by the University or.Minnc-sotil Agricultural Experiment Stiltion (C.F,L. und W.E,R,), K.P.C. is UII Invcstiyutor ol{\textquoteright} The Ho\vurd Hughes Mcdicul Institute.",

year = "1992",

month = apr,

day = "13",

doi = "10.1016/0014-5793(92)80208-X",

language = "English (US)",

volume = "301",

pages = "49--52",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

TY - JOUR

T1 - Structural and functional correlates of a mutation in the malignant hyperthermia-susceptible pig ryanodine receptor

AU - Mickelson, Janies R.

AU - Knudson, C. Michael

AU - Kennedy, Catharine F.H.

AU - Yang, Ding I.

AU - Litterer, Lynn A.

AU - Rempel, William E.

AU - Campbell, Kevin P.

AU - Louis, Charles F.

N1 - Funding Information: .I~~k/,trll~l~T~he a/uthco~rs rwrirshc ,tro/ h.uñk : Dr. Clivc Sl;myhtcr 01 the Howard Huphss Mcdicul loslitutc. University or TL’XIS South-wcstcrn Medical Center, Ibr protein-suqucnciii~ cxpcrtisc. This work was supported by pr;lnts rrom 111~M’u scular Dystrophy Association ol’Amcric;i ;II~ the Niltiunill Pork Producers COUIIC~(lIo J.R.M. und C.F.L.). NIH GM 31382 (to C.F.L.). ;mrl by the University or.Minnc-sotil Agricultural Experiment Stiltion (C.F,L. und W.E,R,), K.P.C. is UII Invcstiyutor ol’ The Ho\vurd Hughes Mcdicul Institute.

PY - 1992/4/13

Y1 - 1992/4/13

N2 - The skeletal muscle ryanodine receptor of malignant hyperthermia-susceptible (MHS) pigs contains a mutation at residue 615 that is highly correlated with various abnormalities in the regulation of sarcoplasmic reticulum (SR) Ca2+ channel activity. In isolated SR membranes the Arg615 to Cys615 ryanodine receptor mutation is now shown to be directly responsible for an altered tryptic peptide map, due to the elimination of the Arg615 cleavage site. Furthermore, trypsin treatment released 86-99 kDa ryanodine receptor fragments encompassing residue 615 from the SR membranes. We conclude that the 86-99 kDa domain containing residue 615 is near the cytoplasmic surface of the ryanodine receptor and likely near important Ca2+ channel regulatory sites.

AB - The skeletal muscle ryanodine receptor of malignant hyperthermia-susceptible (MHS) pigs contains a mutation at residue 615 that is highly correlated with various abnormalities in the regulation of sarcoplasmic reticulum (SR) Ca2+ channel activity. In isolated SR membranes the Arg615 to Cys615 ryanodine receptor mutation is now shown to be directly responsible for an altered tryptic peptide map, due to the elimination of the Arg615 cleavage site. Furthermore, trypsin treatment released 86-99 kDa ryanodine receptor fragments encompassing residue 615 from the SR membranes. We conclude that the 86-99 kDa domain containing residue 615 is near the cytoplasmic surface of the ryanodine receptor and likely near important Ca2+ channel regulatory sites.

KW - Calcium release channel

KW - Malignant hyperthermia

KW - Mutation

KW - Ryanodine receptor

KW - Sarcoplasmic reticulum

UR - http://www.scopus.com/inward/record.url?scp=0026519097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026519097&partnerID=8YFLogxK

U2 - 10.1016/0014-5793(92)80208-X

DO - 10.1016/0014-5793(92)80208-X

M3 - Article

C2 - 1333412

AN - SCOPUS:0026519097

SN - 0014-5793

VL - 301

SP - 49

EP - 52

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

Structural and functional correlates of a mutation in the malignant hyperthermia-susceptible pig ryanodine receptor

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this