CHARACTERIZATION AND LOCALIZATION OF A 77 KDA PROTEIN RELATED TO THE DYSTROPHIN GENE FAMILY

The Duchenne muscular dystrophy gene gives rise to transcripts of seve ral lengths. These mRNAs differ in their coding content and tissue dis tribution. The 14 kb mRNA encodes dystrophin, a 427 kDa protein found in muscle and brain, and the short transcripts described encode DP71, a 77 kDa protein found in various organs. These short transcripts have many features common to the deduced primary structure of dystrophin, especially in the cysteine-rich specific C-terminal domains. The dystr ophin C-terminal domain could be involved in membrane anchorage via th e glycoprotein complex, but such a functional role for these short tra nscript products has yet to be demonstrated. Here we report the first isolation of a short transcript product from saponin-solubilized cardi ac muscle membranes using alkaline buffer and affinity chromatography procedures. This molecule was found to be glycosylated and could be ea sily dissociated from cardiac muscle and other non-muscle tissues such as brain and liver. DP71-specific monoclonal antibody helped to ident ify this molecule as being related to the dystrophin gene family. Immu nofluorescence analysis of bovine or chicken cardiac muscle showed a p eriodic distribution of DP71 in tranverse T tubules and this protein w as co-localized with the dystrophin glycoprotein complex in the Z-disk area.