Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions.

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Research Abstract Details 

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Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Abstract Text:

David C Sheridan,Hiroaki Takekura,Clara Franzini-Armstrong,Kurt G Beam,Paul D Allen,Claudio F Perez,

We have defined regions of the skeletal muscle ryanodine receptor (RyR1) essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and for the organization of DHPR into tetrad arrays by expressing RyR1-RyR3 chimerae in dyspedic myotubes. RyR1-RyR3 constructs bearing RyR1 residues 1-1681 restored wild-type DHPR tetrad arrays and, in part, skeletal-type excitation-contraction (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca(2+) currents (retrograde signaling) to WT RyR1 levels. Within this region, the D2 domain (amino acids 1272-1455), although ineffective on its own, dramatically enhanced the formation of tetrads and EC coupling rescue by constructs that otherwise are only partially effective. These findings suggest that the orthograde signal and DHPR tetrad formation require the contributions of numerous RyR regions. Surprisingly, we found that RyR3, although incapable of supporting EC coupling or tetrad formation, restored a significant level of Ca(2+) current, revealing a functional interaction with the skeletal muscle DHPR. Thus, our data support the hypotheses that (i) the structural/functional link between RyR1 and the skeletal muscle DHPR requires multiple interacting regions, (ii) the D2 domain of RyR1 plays a key role in stabilizing this interaction, and (iii) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein-protein interactions.

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Publishing Authors By Initials

DC Sheridan,H Takekura,C Franzini-Armstrong,KG Beam,PD Allen,CF Perez,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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MEDLINE DATE:

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 19760-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 15

MONTH: 12

YEAR: 2006

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions.

AFFILIATION: University of Colorado Health and Sciences Center, Aurora, CO 80045, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: P01AR44750

ACRONYM: AR

MEDLINETA: Proc Natl Acad Sci U S A

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