Syntrophin isoforms at the neuromuscular junction: Developmental time course and differential localization

The syntrophins are a family of cytoplasmic adapter proteins that associate with dystrophin family proteins and have putative signaling and structural roles at the neuromuscular junction. We have localized the syntrophin fami ly members within the rodent junction from birth to adulthood. alpha-Syntro phin is the only isoform on the postsynaptic membrane at birth. In the adul t, it occurs on the crests of the junctional folds, with utrophin, and in t he troughs, with dystrophin. Surprisingly, neuronal nitric oxide synthase ( nNOS) does not accompany alpha-syntrophin onto the crests. beta 2-Syntrophi n, a junction-specific form, is not present at birth and occurs mainly in t he troughs in the adult, beta 1-Syntrophin is a sarcolemmal form at birth, not concentrated at the junction, and disappears entirely from most fibers by 6 weeks. In positive fibers, junctional beta 1-syntrophin occurs exclusi vely in the troughs. These results suggest that the syntrophin isoforms hav e distinct functions at the junction and show that the known protein-protei n associations of the syntrophins and nNOS in sketetal muscle are not suffi cient to explain their localizations.