Heterogeneity of protein expression within muscle fibers 1

Skeletal muscle fibers are elongated multinucleated cells. Along its length, an individual fiber may contain thousands ofmyonuclei, each controlling protein synthesis within its surrounding cytoplasm. Therefore, a fiber can be considered to be a series of myonuclear domains, each responding to distinct localized signaling mechanisms that may result in differential gene expression within the fiber. This brief review examines phenomena that produce distinct subsets of proteins within different regions of a muscle fiber. These include changes in protein expression associated with activity-induced fiber-type transformation, muscle development, and denervation. Myosin heavychain (MyHC) proteins are fundamental structural and functional components of the muscle fiber. They are represented by different isoforms, each of which is the product of a separate gene that may be differentially expressed during the development of distinct muscle fiber types. We have found that in mature chicken and pigeon pectoralis muscle, the tapered ends offibers contain the neonatal MyHC isoform in addition to the adult isoform found throughout the lengths of the fibers. Examination of serial sections along the length of muscle fibers of chicken pectoralis at different stages of development illustrates that repression of neonatal MyHC isoform expression proceeds as a gradient from the centrally located motor endplate toward the ends of a fiber. In denervated mature fibers, myonuclei furthest from the endplate are the first to reexpress neonatal myosin. We hypothesize that trophic factor(s) emanating from the vicinity of the motor endplate represent a potential localized signaling pathway that may differentially modulate MyHC gene expression along the length of the muscle fiber. Muscle fibers grow in length by the addition of new sarcomeres to their tapered tips, and growing fibers have smaller myonuclear domains (less cytoplasm per nucleus). Additional experiments using chicken pectoralis demonstrated that myonuclear domains are significantly smaller in those areas of the fibers expressing predominantly neonatal myosin. In maturing muscle, the volume of cytoplasm per nucleus is less within the ends of the fibers. Thus, when an increase in the expression of one or more gene products is required within a specific region of the muscle fiber, transcriptional output may be enhanced by the concentration of myonuclei within that region.