Amino acids 1-1,680 of ryanodine receptor type 1 hold critical determinants of skeletal type for excitation-contraction coupling. Role of divergence domain D2

To identify domains of the ryanodine receptor (RyR1) that are functionally relevant for excitation-contraction (EC) coupling in vivo, we have studied the ability of RyR1/RyR3 chimera to rescue skeletal EC coupling in dyspedic myotubes. In this work we show that chimeric receptors containing amino ac...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-10, Vol.278 (41), p.39644-39652
Main Authors: Perez, Claudio F, Mukherjee, Santwana, Allen, Paul D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line
In Vitro Techniques
Kinetics
Membrane Potentials
Molecular Sequence Data
Muscle Contraction - physiology
Muscle, Skeletal - metabolism
Protein Structure, Tertiary
Rabbits
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - physiology
Ryanodine Receptor Calcium Release Channel - chemistry
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - physiology
Sequence Homology, Amino Acid
Signal Transduction
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Summary:To identify domains of the ryanodine receptor (RyR1) that are functionally relevant for excitation-contraction (EC) coupling in vivo, we have studied the ability of RyR1/RyR3 chimera to rescue skeletal EC coupling in dyspedic myotubes. In this work we show that chimeric receptors containing amino acids 1-1,680 of RyR1 were able to render depolarization-induced Ca2+ release to RyR3. Within this region, residues 1,272-1,455, containing divergent domain D2 of RyR1, proved to be a critical element because the absence of this region selectively abolished depolarization-evoked Ca2+ transients without affecting chemically induced activation. Although the D2 domain by itself failed to restore skeletal EC coupling to RyR3, the addition of the D2 region resulted in a dramatic enhancement of EC coupling restored by an RyR3 chimera containing amino acids 1,681-3,770 of RyR1. These results suggest that although the D2 domain of RyR1 plays a key role during EC coupling, additional region(s) from the N-terminal end of RyR1 as well as previously identified regions of the central portion of the receptor are needed in order to allow normal EC coupling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M305160200