γ-Syntrophin scaffolding is spatially and functionally distinct from that of the α/β syntrophins

Amy Alessi, April D. Bragg, Justin M. Percival, Jean Yoo, Douglas E. Albrecht, Stanley C. Froehner, Marvin E. Adams

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 (α, β1, β2) 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 γ-syntrophins do not bind nNOS. In vitro pull-down assays show that the γ-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 γ-syntrophin isoform co-localizes with dystrophin in skeletal muscle. Furthermore, γ-syntrophins do not co-purify with dystrophin isolated from mouse tissue. These data suggest that the interaction of γ-syntrophin with dystrophin is transient and potentially subject to regulatory mechanisms. γ1-Syntrophin is highly expressed in brain and is specifically localized in hippocampal pyramidal neurons, Purkinje neurons in cerebellum, and cortical neurons. γ2-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, γ-syntrophin isoforms localize to the endoplasmic reticulum where they may form a scaffold for signaling and trafficking.

Original languageEnglish (US)
Pages (from-to)3084-3095
Number of pages12
JournalExperimental Cell Research
Volume312
Issue number16
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Keywords

  • Dystrobrevin
  • Dystrophin
  • Neuronal nitric oxide synthase
  • Sarcoplasmic reticulum
  • Syntrophin
  • Utrophin

ASJC Scopus subject areas

  • Cell Biology

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