S U M M A R YCaveolin-3, a muscle-specific member of the caveolin family, is strongly localized to the neuromuscular junction (NMJ) in adult rat muscle fibers, where it co-localizes with ␣ -bungarotoxin staining. In 24-month-old rats, less distinct staining corresponds with the normal aging changes in the NMJ. After denervation, the pattern and intensity of staining begin to break up as early as 3 days, and by 10 days little staining remains. The functional implications of this concentration of caveolin-3 at the NMJ remain obscure, but it is possible that its absence could account for some of the phenotypic characteristics of individuals with caveolin-3 mutations.

No abstract

Elongation factor-1 alpha, (EF-1 alpha), a translation factor involved in peptide chain elongation, is found ubiquitously in all cells. Previously, we identified a highly homologous EF-1 alpha sister gene, S1, whose transcript is found in only three tissues: brain, heart, and muscle, where the tissue-specific expression of S1 is caused by its exclusive presence in cells such as neurons and myocytes. Using sequence-specific synthetic peptides, we have recently produced polyclonal antibodies that can distinguish the protein product of EF-1 alpha from that of its sister, S1. Results of Western blotting show that these two proteins appear in S1-positive muscle tissue in inverse relationship, i.e., when S1 protein is in abundance, EF-1 alpha protein is in contrast in low quantity, and vice versa. During early embryonic stages, EF-1 alpha is the predominant protein species, whereas S1 is hardly detectable. This high EF-1 alpha versus low S1 protein presence undergoes a switch in that by postnatal day 14, EF-1 alpha is scarce whereas S1 is abundant; thus, there is a development-dependent shift of EF-1 alpha/S1 ratio from high to low, and the low EF-1 alpha/S1 ratio is maintained in adulthood. In this report, we describe the reversal of the EF-1 alpha/S1 ratio from low to high during muscle injury (experimentally induced by Marcaine injection), and a return to the original low ratio once the injury is repaired by regeneration. In this injury condition, EF-1 alpha is rapidly upregulated immediately after the Marcaine treatment, possibly reflecting an injury-dependent response of regeneration. The increase of EF-1 alpha corresponds with a decrease of S1 protein presence, thus resulting in a change of EF-1 alpha/S1 ratio from low to high. However, the high EF-1 alpha/S1 ratio eventually reverts to low, when regeneration-associated proliferation ceases, and fully differentiated myotubes are reestablished in the injured cells. This result shows that: (1) a high EF-1 alpha/S1 ratio is an early molecular diagnostic marker for injury-elicited regeneration; and (2) when injury repair is accomplished, there is a reversion to the low EF-1 alpha/S1 ratio, reflecting the restoration of the muscle fiber to the preinjury functional status. Results presented here not only show that a high EF-1 alpha/S1 ratio is a molecular marker for injured muscle, but also reveal the underpinning translational regulation in muscle during injury.