ACTININ-ASSOCIATED LIM PROTEIN - IDENTIFICATION OF A DOMAIN INTERACTION BETWEEN PDZ AND SPECTRIN-LIKE REPEAT MOTIFS

PDZ motifs are protein-protein interaction domains that often bind to COOH-terminal peptide sequences. The two PDZ proteins characterized in skeletal muscle, syntrophin and neuronal nitric oxide synthase, occur in the dystrophin complex, suggesting a role for PDZ proteins in musc ular dystrophy. Here, we identify actinin-associated LIM protein (ALP) , a novel protein in skeletal muscle that contains an NH2-terminal PDZ domain and a COOH-terminal LIM motif. ALP is expressed at high levels only in differentiated skeletal muscle, while an alternatively splice d form occurs at low levels in the heart. ALP is not a component of th e dystrophin complex, but occurs in association with alpha-actinin-2 a t the Z lines of myofibers. Biochemical and yeast two-hybrid analyses demonstrate that the PDZ domain of ALP binds to the spectrin-like moti fs of alpha-actinin-2, defining a new mode for PDZ domain interactions . Fine genetic mapping studies demonstrate that ALP occurs on chromoso me 4q35, near the heterochromatic locus that is mutated in fascioscapu lohumeral muscular dystrophy.