Figure 3.

Model of the STAC3 interactions in the skeletal muscle excitation‐contraction (EC) coupling apparatus. STAC3 has been demonstrated to establish two discrete interactions with the dihydropyridine receptor (DHPR): its C1 domain interacts with the IQ domain in the C‐terminus, and the SH3‐1 domain interacts with the IPR motif in the II–III loop of the DHPR. Here, we provide evidence of a third, hitherto unidentified, interaction, which anchors STAC3 in the triad junctions independent of the DHPR. We propose that it is established by the SH3‐2 domain. Because of the crucial role of STAC3 in EC coupling and because no additional proteins are necessary to restore voltage‐induced calcium release in heterologous cells, STAC3 may thus directly couple the DHPR with the RyR1. RyR1, ryanodine receptor [Color figure can be viewed at wileyonlinelibrary.com]