Expression and localization of RGS9-2/Gβ5/R7BP complex In Vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases
Expression and localization of RGS9-2/Gβ5/R7BP complex In Vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases
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DOI：
10.1523/jneurosci.3884-07.2007
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发表时间：
2007-12-19
影响因子：
5.3
通讯作者：
Martemyanov, Kirill A.
中科院分区：
文献类型：
--
作者：
Anderson, Garret R.;Lujan, Rafael;Martemyanov, Kirill A.
RGS 9 -2是G蛋白信号家族的一员，是通过神经元多巴胺和阿片样G蛋白偶联受体进行信号传导的重要调节剂。最近的研究结果表明，RGS 9 -2的丰度决定了纹状体中运动和奖励系统中信号传导的敏感性。在这项研究中，我们报告了在体内设定RGS 9 -2浓度的机制，从而控制该区域的G蛋白信号敏感性。我们发现，RGS 9 -2具有特定的降解决定簇，其靶向其被溶酶体半胱氨酸蛋白酶组成性破坏。通过结合伴侣R7结合蛋白（R7 BP）屏蔽这些决定簇控制RGS 9 -2在翻译后水平的表达。此外，与神经元中的R7 BP结合将RGS 9 -2靶向特定的细胞内区室，即突触后密度。在整个个体发育过程中实施该机制确保了RGS 9 -2/5型G蛋白β亚基/R7 BP复合物在突触后位点的表达与成熟突触处增加的信号传导需求一致。
A member of regulator of G-protein signaling family, RGS9-2, is an essential modulator of signaling through neuronal dopamine and opioid G-protein-coupled receptors. Recent findings indicate that the abundance of RGS9-2 determines sensitivity of signaling in the locomotor and reward systems in the striatum. In this study we report the mechanism that sets the concentration of RGS9-2 in vivo, thus controlling G-protein signaling sensitivity in the region. We found that RGS9-2 possesses specific degradation determinants which target it for constitutive destruction by lysosomal cysteine proteases. Shielding of these determinants by the binding partner R7 binding-protein (R7BP) controls RGS9-2 expression at the posttranslational level. In addition, binding to R7BP in neurons targets RGS9-2 to the specific intracellular compartment, the postsynaptic density. Implementation of this mechanism throughout ontogenetic development ensures expression of RGS9-2/type 5 G-protein beta subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.