BEACH蛋白LRBA促进异三聚体G蛋白高尔夫向嗅纤毛的定位。,Scientific Reports

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BEACH蛋白LRBA促进异三聚体G蛋白高尔夫向嗅纤毛的定位。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Aug-16 , DOI: 10.1038/s41598-017-08543-4
Stefan Kurtenbach , Andreas Gießl , Siv Strömberg , Jan Kremers , Jenny Atorf , Sebastian Rasche , Eva M. Neuhaus , Denis Hervé , Johann Helmut Brandstätter , Esther Asan , Hanns Hatt , Manfred W. Kilimann

BEACH结构域蛋白参与膜蛋白运输和人类疾病，但其分子机制尚不清楚。BEACH蛋白LRBA与免疫反应和细胞增殖有关，人LRBA突变会导致严重的免疫缺陷。在这里，我们报告了LRBA基因敲除小鼠免疫系统以外的第一个功能和分子表型：嗅觉受损，表现为电嗅觉反应幅度降低，食物寻找效率受损和嗅球变小。LRBA在野生型小鼠的嗅觉和犁鼻化学感受神经元中显着表达。在LRBA-KO嗅觉障碍是通过显着地降低所有三个亚基的浓度（野生型水平的20-40％）解释α _OLF，β ₁，γ嗅觉神经元感觉纤毛中的₁₃种嗅觉异三聚体G蛋白G _olf。相反，纤毛的形态和嗅纤毛的许多其他蛋白质的浓度没有受到或仅有轻微的影响。LRBA在感光细胞中也高表达，感光细胞是另一种具有特殊感觉纤毛和异源三聚体G蛋白信号的细胞。但是，LRBA-KO并没有削弱视觉功能。据我们所知，这是首次观察到BEACH蛋白对于脂质锚定蛋白和睫状蛋白的有效亚细胞定位是必需的。

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The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia.

BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs. LRBA is prominently expressed in olfactory and vomeronasal chemosensory neurons of wild-type mice. Olfactory impairment in the LRBA-KO is explained by markedly reduced concentrations (20-40% of wild-type levels) of all three subunits α_olf, β₁ and γ₁₃ of the olfactory heterotrimeric G-protein, G_olf, in the sensory cilia of olfactory neurons. In contrast, cilia morphology and the concentrations of many other proteins of olfactory cilia are not or only slightly affected. LRBA is also highly expressed in photoreceptor cells, another cell type with a specialized sensory cilium and heterotrimeric G-protein-based signalling; however, visual function appeared unimpaired by the LRBA-KO. To our knowledge, this is the first observation that a BEACH protein is required for the efficient subcellular localization of a lipid-anchored protein, and of a ciliary protein.

更新日期：2017-08-16

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