Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 39644-39652 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 278 |
| Issue number | 41 |
| DOIs | |
| State | Published - Oct 10 2003 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
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. / Perez, Claudio F.; Mukherjee, Santwana; Allen, Paul D.
In: Journal of Biological Chemistry, Vol. 278, No. 41, 10.10.2003, p. 39644-39652.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Perez, Claudio F.
AU - Mukherjee, Santwana
AU - Allen, Paul D.
PY - 2003/10/10
Y1 - 2003/10/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0141994822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141994822&partnerID=8YFLogxK
U2 - 10.1074/jbc.M305160200
DO - 10.1074/jbc.M305160200
M3 - Article
C2 - 12900411
AN - SCOPUS:0141994822
VL - 278
SP - 39644
EP - 39652
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 41
ER -