γ-Syntrophin scaffolding is spatially and functionally distinct from that of the α/β syntrophins
γ-Syntrophin scaffolding is spatially and functionally distinct from that of the α/β syntrophins
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DOI：
10.1016/j.yexcr.2006.06.019
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发表时间：
2006-10-01
影响因子：
3.7
通讯作者：
Adams, Marvin E.
中科院分区：
文献类型：
--
作者：
Alessi, Amy;Bragg, April D.;Adams, Marvin E.
突触营养蛋白是具有多个蛋白质相互作用结构域的支架蛋白家族，所述蛋白质相互作用结构域将信号蛋白连接至肌营养不良蛋白家族成员。三种最具特征的促突触蛋白（α，β 1，β 2）中的每一种都含有一个PDZ结构域，该结构域结合一组独特的信号蛋白，包括激酶、离子和水通道以及神经元一氧化氮合酶（nNOS）。γ-突触营养蛋白的PDZ结构域不结合nNOS。体外下拉分析显示，γ-突触营养蛋白可以结合肌营养不良蛋白，但对肌营养不良蛋白家族成员的突触营养蛋白结合位点具有独特的偏好。尽管它们能够在体外结合肌营养不良蛋白，但γ-突触营养蛋白同种型都不与肌营养不良蛋白在骨骼肌中共定位。此外，γ-突触营养蛋白不与从小鼠组织分离的肌营养不良蛋白共纯化。这些数据表明，γ-syntrophin与肌营养不良蛋白的相互作用是短暂的，并可能受到监管机制。γ 1-Syntrophin在大脑中高度表达，并特异性定位于海马锥体神经元、小脑浦肯野神经元和皮质神经元。γ 2-促突触蛋白在包括骨骼肌在内的许多组织中表达，其中仅在神经肌肉接头下方的突触下空间中发现。在神经元和肌肉中，γ-突触营养蛋白亚型定位于内质网，在那里它们可以形成用于信号传导和运输的支架。(c)2006年爱思唯尔公司All rights reserved.
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, beta 1, beta 2) 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. gamma 1-Syntrophin is highly expressed in brain and is specifically localized in hippocampal pyramidal neurons, Purkinje neurons in cerebellum, and cortical neurons. gamma 2-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. (c) 2006 Elsevier Inc. All rights reserved.