Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of sp d cells such as muscle. It has been previously shown that the dystrophin-asocited protein Al (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic (a-Al) and a distinct basic ((-Al) component. Partial peptide sequence of the Al complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform ofAl. This cDNA encodes a basic Al isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinctmRNA speciesof5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of our human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human homologue of the published mouse syntrophin 2. We have mapped the human basic component of Al and EST25263 genes to chromosomes 8q23-24 and 16, respectively.Dystrophin is the protein product of a large X chromosomeencoded gene that, when defective, can lead to Duchenne and Becker muscular dystrophies (1). When dystrophin is purified from skeletal muscle membranes by absorption onto wheat germ agglutinin-Sepharose, it is found in association with a large oligomeric complex of membrane glycoproteins, the dystrophin-associated glycoprotein (DAG) complex (DAGC) (2). The dystrophin-associated proteins (DAPs) named Al (62 kDa), A2 (52 kDa), A3 (43 kDa), A4 (36 kDa), and A5 (24 kDa), respectively, correspond to the 59-kDa DAP (59-DAP), 50-kDa DAG, 43-kDa DAG, 35-kDa DAG, and 25-kDa DAP reported elsewhere (3, 4). In addition, AO (94 kDa) is distinct from the 156-kDa DAG; the latter stains weakly with Coomp-;sie brilliant blue *1F These proteins, together with dystrcy'in, a-* thought tv participate in the actin-based membrane cytoskeleton of the muscle cell to maintain its stability. The 156-kDa DAG, dystroglycan, biochemically interacts with the extracellular component laminin, functionally implicating dystrophin and the DAGC as a link between the extracellular matrix and the membrane cytoskeleton (5).The site of interaction between dystrophin and the DAGC has been mapped to within the cysteine-rich domain and the first half of the C-terminal domain of dystrophin (6, 7), suggesting that the DAGC may also interact with the C-terminal dystrophin protein of 71 kDa (Dp7l) (8) and the autosomal near-relative of dystrophin, dystrophin-related protein (DRP or utrophin) (9). Al/59-DAP and its Torpedo homologue, 58K (10), have recently been shown by two separate groups to coimmunoprecipitate with dystrophin (11,12). The Torpedo 58K and two homologues in mouse have recently been cloned and named syntrophins (13).A separate study has shown that purified Al/59-DAP consists ofan acidic (a-Al) and a basic ((3-Al) Al population, which can be discriminated by a monoclonal antibody (14 cDNA C...

The cellular localization of the peptide neurotransmitter proctolin was determined for larvae of the fruitfly Drosophila melanogaster. Proctolin was recovered from the CNS, hindgut, and segmental bodywall using reverse-phase HPLC, and characterized by bioassay, immunoassay, and enzymatic analysis. A small, stereotyped population of proctolin-immunoreactive neurons was found in the larval CNS. Several of the identified neurons may be efferents. In the periphery, proctolin-immunoreactive neuromuscular endings were identified on both visceral and skeletal muscle fibers. On the hindgut, the neuropeptide is associated with endings on intrinsic circular muscle fibers. We propose that the hindgut muscle fibers are innervated by central neurons homologous to previously described proctolinergic efferents of grasshoppers. The segmental bodywall innervation consists of a pattern of segment-specific junctions on several singly identifiable muscle fibers. While it is generally accepted that Drosophila muscle fibers are innervated by glutamatergic motoneurons, our data indicate that a specialized subset of muscle fibers are also innervated by peptidergic efferents.

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