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首页> 外文期刊>BMC Neuroscience >Human neuronal stargazin-like proteins, γ 2 , γ 3 and γ 4 ; an investigation of their specific localization in human brain and their influence on Ca V 2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.
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Human neuronal stargazin-like proteins, γ 2 , γ 3 and γ 4 ; an investigation of their specific localization in human brain and their influence on Ca V 2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.

机译：人神经元类stargazin样蛋白γ2，γ3和γ4;对它们在人脑中的特定定位及其对非洲爪蟾卵母细胞中表达的Ca V 2.1电压依赖性钙通道的影响的研究。

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Background Stargazin (γ2) and the closely related γ3, and γ4 transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC) γ subunits and transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA) receptor regulatory proteins (TARPs). In this investigation, we examined the distribution patterns of the stargazin-like proteins γ2, γ3, and γ4 in the human central nervous system (CNS). In addition, we investigated whether human γ2 or γ4 could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes. Results The mRNA encoding human γ2 is highly expressed in cerebellum, cerebral cortex, hippocampus and thalamus, whereas γ3 is abundant in cerebral cortex and amygdala and γ4 in the basal ganglia. Immunohistochemical analysis of the cerebellum determined that both γ2 and γ4 are present in the molecular layer, particularly in Purkinje cell bodies and dendrites, but have an inverse expression pattern to one another in the dentate cerebellar nucleus. They are also detected in the interneurons of the granule cell layer though only γ2 is clearly detected in granule cells. The hippocampus stains for γ2 and γ4 throughout the layers of the every CA region and the dentate gyrus, whilst γ3 appears to be localized particularly to the pyramidal and granule cell bodies. When co-expressed in Xenopus oocytes with a CaV2.1/β4 VDCC complex, either in the absence or presence of an α2δ2 subunit, neither γ2 nor γ4 significantly modulated the VDCC peak current amplitude, voltage-dependence of activation or voltage-dependence of steady-state inactivation. Conclusion The human γ2, γ3 and γ4 stargazin-like proteins are detected only in the CNS and display differential distributions among brain regions and several cell types in found in the cerebellum and hippocampus. These distribution patterns closely resemble those reported by other laboratories for the rodent orthologues of each protein. Whilst the fact that neither γ2 nor γ4 modulated the properties of a VDCC complex with which they could associate in vivo in Purkinje cells adds weight to the hypothesis that the principal role of these proteins is not as auxiliary subunits of VDCCs, it does not exclude the possibility that they play another role in VDCC function.
机译：背景Stargazin（γ 2 ）和密切相关的γ 3 和γ 4 跨膜蛋白是可能充当分子的蛋白家族的一部分神经元电压依赖性钙通道（VDCC）γ亚基和跨膜α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体调节蛋白（TARP）。在这项研究中，我们研究了星形胶质蛋白样蛋白γ 2 ，γ 3 和γ 4 在人中枢神经中的分布模式。系统（CNS）。此外，我们研究了人类γ 2 或γ 4 是否可以调节非洲爪蟾卵母细胞中瞬时表达的神经元VDCC复合物的电生理特性。结果编码人γ 2 的mRNA在小脑，大脑皮层，海马和丘脑中高表达，而γ 3 在大脑皮层，杏仁核和γ 4中丰富。 在基底节。小脑的免疫组织化学分析确定，γ 2 和γ 4 均存在于分子层中，特别是在浦肯野细胞体和树突中，但与一种表达形式相反另一个在齿状小脑核中。尽管在颗粒细胞中仅清楚地检测到γ 2 ，但它们也在颗粒细胞层的中间神经元中被检测到。在每个CA区域和齿状回的整个层中，海马的γ 2 和γ 4 染色，而γ 3 似乎是局部的特别是锥体细胞和颗粒细胞。当与Ca V 2.1 /β 4 VDCC复合体在非洲爪蟾卵母细胞中共表达时，无论是否存在α2δ 2 亚基γ 2 和γ 4 均未显着调节VDCC峰值电流幅度，激活的电压依赖性或稳态失活的电压依赖性。结论仅在中枢神经系统中检测到人γ 2 ，γ 3 和γ 4 stargazin样蛋白，并在脑区和脑区显示出差异分布。在小脑和海马中发现了几种细胞类型。这些分布模式与其他实验室报告的每种蛋白质的啮齿类动物直向同源物非常相似。尽管γ 2 和γ 4 均未调节VDCC络合物的性质，但它们可以在体内与Purkinje细胞缔合，这增加了这一假说的重要性，这些蛋白质中的一部分不是VDCC的辅助亚基，也不排除它们在VDCC功能中起其他作用的可能性。

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