Fig. 9

Alternative splicing produces SSPN, μSPN, and nSPN with distinct subcellular membrane localizations. The schematic diagram illustrates the sarcolemma, SR, and T-tubule membranes and their placement with respect to the muscle sarcomere. The SR has three distinct regions: a triadic region flanking the T-tubules (triadic SR), a region across the Z-line (ZSR), and a region across the M-line (LSR). Note that the ZSR and LSR are represented in light SR fractions, while the triadic SR is represented in the heavy SR fractions. The upper left enlargement represents a schematic diagram showing localization of SSPN at the sarcolemma, where it is a core component of the DGC. SSPN is represented as a four-transmembrane-spanning protein with the color scheme as described in Fig. 1. The sarcoglycans (α-, β-, γ-, δ-SGs; orange) are depicted as transmembrane oval shapes. The SGs and SSPN form a tight subcomplex within the DGC. Dystrophin (not shown) interacts with β-DG on the cytoplasmic face of the sarcolemma membrane and provides linkage to the actin cytoskeleton. Dystroglycan (not shown) serves as a receptor for extracellular matrix ligands. The enlargement on the upper right represents a schematic illustration of the SR membranes where nSPN and μSPN (color scheme as described in Fig. 1) are enriched and associate with a subset of the SGs (δ-SG, δ-SG3, and γ-SG; orange) [26, 50]. Triadic SR regions contain δ-SG3, nSPN, and μSPN (lower enlargement), but lack δ-SG and γ-SG as previously described [26, 50]. Data from two-photon laser scanning microscopy reveals that nSPN is mostly associated with the ZSR and the triadic SR, and only minimally with the LSR. While protein expression of nSPN, μSPN, and SG isoforms in the SR is demonstrated, it is unclear whether these proteins form a subcomplex within these intracellular membrane structures, which will be the focus of future studies