Functional importance of polymerization and localization of calsequestrin in C. elegans.
Dual roles of calsequestrin (CSQ-1) being the Ca2+ donor and Ca2+ acceptor make it an excellent Ca2+-buffering protein within the sarcoplasmic reticulum (SR). We have isolated and characterized a calsequestrin (csq-1)-null mutant in Caenorhabditis elegans. To our surprise, this mutant csq-1(jh109) showed no gross defects in muscle development or function but, however, is highly sensitive to perturbation of Ca2+ homeostasis. By taking advantage of the viable null mutant, we investigated the domains of CSQ-1 that are important for polymerization and cellular localization, and required for its correct buffering functions. In transgenic animals rescued with various CSQ-1 constructs, the in vivo patterns of polymerization and localization of several mutated calsequestrins were observed to correlate with the structure-function relationship. Our results suggest that polymerization of CSQ-1 is essential but not sufficient for correct cellular localization and function of CSQ-1. In addition, direct interaction between CSQ-1 and the ryanodine receptor (RyR) was found for the first time, suggesting that the cellular localization of CSQ-1 in C. elegans is indeed modulated by RyR through a physical interaction.
Cho
Jeong Hoon
JH
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea. joohong@gist.ac.kr
Ko
Kyung Min
KM
Singaruvelu
Gunasekaran
G
Lee
Wonhae
W
Kang
Gil Bu
GB
Rho
Seong-Hwan
SH
Park
Byung-Jae
BJ
Yu
Jae-Ran
JR
Kagawa
Hiroaki
H
Eom
Soo Hyun
SH
Kim
Do Han
DH
Ahnn
Joohong
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D017353:Gene Deletion; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D002155:Calsequestrin; D011108:Polymers; D019837:Ryanodine Receptor Calcium Release Channel; D004533:Egtazic Acid; D002118:Calcium