gamma-Syntrophin scaffolding is spatially and functionally distinct from that of the alpha/beta syntrophins.
The syntrophins are a family of scaffolding proteins with multiple protein interaction domains that link signaling proteins to dystrophin family members. Each of the three most characterized syntrophins (alpha, beta1, beta2) contains a PDZ domain that binds a unique set of signaling proteins including kinases, ion and water channels, and neuronal nitric oxide synthase (nNOS). The PDZ domains of the gamma-syntrophins do not bind nNOS. In vitro pull-down assays show that the gamma-syntrophins can bind dystrophin but have unique preferences for the syntrophin binding sites of dystrophin family members. Despite their ability to bind dystrophin in vitro, neither gamma-syntrophin isoform co-localizes with dystrophin in skeletal muscle. Furthermore, gamma-syntrophins do not co-purify with dystrophin isolated from mouse tissue. These data suggest that the interaction of gamma-syntrophin with dystrophin is transient and potentially subject to regulatory mechanisms. gamma1-Syntrophin is highly expressed in brain and is specifically localized in hippocampal pyramidal neurons, Purkinje neurons in cerebellum, and cortical neurons. gamma2-Syntrophin is expressed in many tissues including skeletal muscle where it is found only in the subsynaptic space beneath the neuromuscular junction. In both neurons and muscle, gamma-syntrophin isoforms localize to the endoplasmic reticulum where they may form a scaffold for signaling and trafficking.
Alessi
Amy
A
Department of Physiology and Biophysics, University of Washington, 1959 Pacific ST NE, Seattle, WA 98195-7290, USA.
Bragg
April D
AD
Percival
Justin M
JM
Yoo
Jean
J
Albrecht
Douglas E
DE
Froehner
Stanley C
SC
Adams
Marvin E
ME
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D016189:Dystrophin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011689:Purkinje Cells / Q000166:cytology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D020033:Protein Isoforms; C091824:syntrophin; D052248:Nitric Oxide Synthase Type I