title: Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs.
abstract: 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 muscular 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 spliced form occurs at low levels in the heart. ALP is not a component of the dystrophin complex, but occurs in association with alpha-actinin-2 at the Z lines of myofibers. Biochemical and yeast two-hybrid analyses demonstrate that the PDZ domain of ALP binds to the spectrin-like motifs of alpha-actinin-2, defining a new mode for PDZ domain interactions. Fine genetic mapping studies demonstrate that ALP occurs on chromosome 4q35, near the heterochromatic locus that is mutated in fascioscapulohumeral muscular dystrophy.
authors.affiliation: Department of Physiology, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: H
authors.initials: H
authors.lastname: Xia
authors.forename: S T
authors.initials: ST
authors.lastname: Winokur
authors.forename: W L
authors.initials: WL
authors.lastname: Kuo
authors.forename: M R
authors.initials: MR
authors.lastname: Altherr
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D014644:Genetic Variation; D006801:Humans; D007621:Karyotyping; D060588:LIM Domain Proteins; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry*
chemical_list: D060588:LIM Domain Proteins; D008840:Microfilament Proteins; C108834:PDLIM3 protein, human; C484641:Pdlim3 protein, rat; D000185:Actinin; D013049:Spectrin