| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print November 18, 2003
Dept. of Biochemical Pharmacology, University of Innsbruck, Innsbruck A-6020
Corresponding Author: manfred.grabner{at}uibk.ac.at
Residues L720-L764 within the II-III loop of the skeletal muscle dihydropyridine receptor (DHPR)
J. Biol. Chem, 10.1074/jbc.M307538200
Submitted on July 14, 2003
Revised on November 18, 2003
Accepted on November 18, 2003
Structural requirements of the dihydropyridine receptor
1S II-III loop for skeletal-type excitation-contraction coupling
1S subunit represent a critical domain for the orthograde, excitation-contraction (EC) coupling as well as for the retrograde, DHPR L-current enhancing coupling with the ryanodine receptor (RyR1). To better understand the molecular mechanism underlying this bidirectional DHPR-RyR1 signaling interaction we analyzed the critical domain to the single amino acid level. To this end constructs based on the highly dissimilar house fly DHPR II-III loop in an otherwise skeletal DHPR as an interaction-inert sequence background were expressed in dysgenic (1S-null) myotubes for simultaneously recordings of depolarization-induced intracellular Ca2+ transients (orthograde coupling) and whole-cell Ca2+ currents (retrograde coupling). In the minimal skeletal II-III loop sequence (D734-D748) required for full bidirectional coupling, eight amino acids heterologous between skeletal and cardiac DHPR were exchanged for the corresponding cardiac residues. Four of these skeletal-specific residues (A739, F741, P742, D744) turned out to be essential for orthograde, two of them (A739, F741) for retrograde coupling, indicating that orthograde coupling does not necessarily correlate with retrograde signaling. Secondary structure predictions of the critical domain show that an -helical (cardiac sequence-type) conformation of a cluster of negatively charged residues (D744-E751 of 1S) corresponds with significantly reduced Ca2+ transients. Conversely, a predicted random coil structure (skeletal sequence-type) seems to be prerequisite for the restoration of skeletal-type EC coupling. Thus, not only the primary but also the secondary structure of the critical domain is an essential determinant of the tissue-specific mode of EC coupling.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. A. Bannister, M. Grabner, and K. G. Beam The {alpha}1S III-IV Loop Influences 1,4-Dihydropyridine Receptor Gating but Is Not Directly Involved in Excitation-Contraction Coupling Interactions with the Type 1 Ryanodine Receptor J. Biol. Chem., August 22, 2008; 283(34): 23217 - 23223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Lorenzon and K. G. Beam Accessibility of Targeted DHPR Sites to Streptavidin and Functional Effects of Binding on EC Coupling J. Gen. Physiol., September 24, 2007; 130(4): 379 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hirata, T. Watanabe, J. Hatakeyama, S. M. Sprague, L. Saint-Amant, A. Nagashima, W. W. Cui, W. Zhou, and J. Y. Kuwada Zebrafish relatively relaxed mutants have a ryanodine receptor defect, show slow swimming and provide a model of multi-minicore disease Development, August 1, 2007; 134(15): 2771 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Anderson, X. Altafaj, Z. Zheng, Z.-M. Wang, O. Delbono, M. Ronjat, S. Treves, and F. Zorzato The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1 J. Cell Sci., May 15, 2006; 119(10): 2145 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Carbonneau, D. Bhattacharya, D. C. Sheridan, and R. Coronado Multiple Loops of the Dihydropyridine Receptor Pore Subunit Are Required for Full-Scale Excitation-Contraction Coupling in Skeletal Muscle Biophys. J., July 1, 2005; 89(1): 243 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Takekura, C. Paolini, C. Franzini-Armstrong, G. Kugler, M. Grabner, and B. E. Flucher Differential Contribution of Skeletal and Cardiac II-III Loop Sequences to the Assembly of Dihydropyridine-Receptor Arrays in Skeletal Muscle Mol. Biol. Cell, December 1, 2004; 15(12): 5408 - 5419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Lorenzon, C. S. Haarmann, E. E. Norris, S. Papadopoulos, and K. G. Beam Metabolic Biotinylation as a Probe of Supramolecular Structure of the Triad Junction in Skeletal Muscle J. Biol. Chem., October 15, 2004; 279(42): 44057 - 44064. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
