Role of ryanodine receptors in the assembly of calcium release units in skeletal muscle

Feliciano Protasi, Clara Franzini-Armstrong, Paul D. Allen

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

In muscle cells, excitation-contraction (e-c) coupling is mediated by 'calcium release units', junctions between the sarcoptasmic reticulum (SR) and exterior membranes. Two proteins, which face each other, are known to functionally interact in those structures: the ryanodine receptors (RyRs), or SR calcium release channels, and the dihydropyridine receptors (DHPRs), or L- type calcium channels of exterior membranes. In skeletal muscle, DHPRs form tetrads, groups of four receptors, and tetrads are organized in arrays that face arrays of feet (or RyRs). Triadin is a protein of the SR located at the SR-exterior membrane junctions, whose role is not known. We have structurally characterized calcium release units in a skeletal muscle cell line (1B5) lacking Ry1R. Using immunohistochemistry and freeze fracture electron microscopy, we find that DHPR and triadin are clustered in foci in differentiating 1B5 cells. Thin section electron microscopy reveals numerous SR-exterior membrane junctions lacking foot structures (dyspedic). These results suggest that components other than Ry1Rs are responsible for targeting DHPRs and triadin to junctional regions. However, DHPRs in 1 B5 cells are not grouped into tetrads as in normal skeletal muscle cells suggesting that anchoring to Ry1Rs is necessary for positioning DHPRs into ordered arrays of tetrads. This hypothesis is confirmed by finding a 'restoration of tetrads' in junctional domains of surface membranes after transfection of 1B5 cells with cDNA encoding for Ry1R.

Original languageEnglish (US)
Pages (from-to)831-842
Number of pages12
JournalJournal of Cell Biology
Volume140
Issue number4
DOIs
StatePublished - Feb 23 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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