NEURONAL NITRIC-OXIDE SYNTHASE-MU, AN ALTERNATIVELY SPLICED ISOFORM EXPRESSED IN DIFFERENTIATED SKELETAL-MUSCLE

Nitric oxide (NO) functions as a molecular mediator in numerous proces ses in cellular development and physiology. Differential expression an d regulation of a family of three NO synthase (NOS) gene products help achieve this diversity of action. Previous studies identify post- tra nslational modification and interaction of NOS with specific protein t argets as tissue-specific modes of regulation, Here, we show that alte rnative splicing specifically regulates neuronal NOS (nNOS, type I) in striated muscle. nNOS in skeletal muscle is slightly more massive tha n nNOS from brain owing to a 102-base pair (34-amino acid) alternative ly spliced segment between exons 16 and 17. Following purification, th is novel nNOS mu isoform has similar catalytic activity to that of nNO S expressed in cerebellum. nNOS mu appears to function exclusively in differentiated muscle as its expression occurs coincidentally with myo tube fusion in culture. An isoform-specific antibody detects nNOS mu p rotein only in skeletal muscle and heart, This study identifies altern ative splicing as a means for tissue-specific regulation of nNOS and r eports the first additional protein sequence for a mammalian NOS since the original cloning of the gene family.