Protein targeting to the plasma membrane of adult skeletal muscle fiber: An organized mosaic of functional domains

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and mu scle-tendon junctions. We analyzed the organization of these domains in rel ation to defined surface markers, beta -dystroglycan, dystrophin, and caveo lin-3, These markers were shown to exhibit highly organized arrays along th e length of the fiber. Caveolin-3 and beta -dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both marker s left transverse tubule openings clear. This labeling pattern revealed mic rodomains over the entire plasma membrane with the exception of the neuromu scular and muscle-tendon junctions which formed distinct demarcated macrodo mains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta -dystroglycan domains. The domains identified with these markers w ere examined with respect to targeting of viral proteins and other expresse d domain-specific markers, We found that each marker protein was targeted t o distinct microdomains, The macrodomains were intensely labeled with all o ur markers. Replacing the cytoplasmic tail of the vesicular stomatitis viru s glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surfac e may be generated by targeting pathways requiring specific sorting informa tion but this trafficking is different from the conventional apical-basolat eral division. (C) 2001 Academic Press.