gamma-Syntrophin scaffolding is spatially and functionally distinct from that of the alpha/beta syntrophins |
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Authors: | Alessi Amy Bragg April D Percival Justin M Yoo Jean Albrecht Douglas E Froehner Stanley C Adams Marvin E |
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Institution: | Department of Physiology and Biophysics, University of Washington, 1959 Pacific ST NE, Seattle, WA 98195-7290, USA. |
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Abstract: | 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. |
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Keywords: | PH pleckstrin homology PDZ domain first identified in PSD-95Discs-large and ZO-1 RACE rapid amplification of cDNA ends Pab polyclonal antibody Mab Monoclonal antibody GST glutathione S-transferase nNOS neuronal nitric oxide synthase DGKζ diacylglycerol kinase ζ PBS phosphate buffered saline BSA bovine serum albumin SBS syntrophin binding site |
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