Identification of α-Syntrophin Binding to Syntrophin Triplet, Dystrophin, and Utrophin

Abstract

Syntrophin represents three cytoplasmic components of the dystrophin-glycoprotein complex that links the cytoskeleton to the extracellular matrix in skeletal muscle. alpha-Syntrophin has now been translated in vitro and shown to associate directly with all three components of the syntrophin triplet and with dystrophin. The in vitro translated 71-kDa non-muscle dystrophin isoform, containing the cystein-rich/C-terminal domain, can also interact with the syntrophin triplet. The syntrophin binding motif in dystrophin was localized to exons 73 and 74 including amino acids 3447-3481 by comparing the interactions of alpha-syntrophin and seven overlapping human dystrophin fusion proteins. More than one syntrophin interaction site in this binding motif was suggested. alpha-Syntrophin also interacts directly with a C-terminal utrophin fusion protein. alpha-Syntrophin is localized to the muscle sarcolemma as well as to the neuromuscular junction in control mouse muscle. However, similar to utrophin, alpha-syntrophin is only present at the neuromuscular junction in mdx mouse muscle in which dystrophin is absent. Our data suggest that alpha-syntrophin binds all syntrophin isoforms, and syntrophin directly interacts with dystrophin through more than one binding site in dystrophin exons 73 and 74 including amino acids 3447-3481.

Direct binding of Torpedo syntrophin to dystrophin and the 87 kDa dystrophin homologue

“…Recent work from several laboratories has shown that mammalian syntrophins are capable of binding directly to different members of the dystrophin family [24][25][26][27] Torpedo ~-syntrophin also bound to an additional member of the dystrophin family, the 87K postsynaptic protein. The 87K protein has 27% amino acid identity to dystrophin scattered throughout the CRCT domain ( [14], see also Fig.…”

Characterization of the dystrophin‐syntrophin interaction using the two‐hybrid system in yeast

“…Syntrophins are a heterogeneous group of phosphorylated 58-59 kDa proteins encoded by at least three different genes which are classified in acidic (ct) and basic ([~) components and show a different expression pattern [5]. Alpha-1 syntrophin, which has been cloned in mouse [6] and rabbit [7], is abundantly expressed in skeletal muscle. Beta-1 syntrophin, which has been isolated in human, is ubiquitously expressed but at lower levels in brain and heart than in other tissues [8].…”

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

“…In skeletal muscle, ␣1-and ␤1-syntrophin are found on the sarcolemma and are relatively concentrated at the neuromuscular junction (NMJ), whereas ␤2-syntrophin is concentrated at the NMJ but barely detectable on the sarcolemma (Peters et al, 1994(Peters et al, , 1997. Syntrophins bind directly to the C-terminal domain of dystrophin and the dystrophin-related proteins utrophin and dystrobrevin Ahn and Kunkel, 1995;Dw yer and Froehner, 1995;Yang et al, 1995;Ahn et al, 1996). The absence of dystrophin in Duchenne muscular dystrophy (DMD) and the md x mouse leads to a dramatic reduction in sarcolemmal syntrophin, although the syntrophins remain concentrated at the NMJ (Butler et al, 1992;Peters et al 1994Peters et al , 1997Yang et al, 1995).…”