Protein-4.1G-Mediated Membrane Trafficking Is Essential for Correct Rod Synaptic Location in the Retina and for Normal Visual Function.
Protein-4.1G-Mediated Membrane Trafficking Is Essential for Correct Rod Synaptic Location in the Retina and for Normal Visual Function.
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DOI：
10.1016/j.celrep.2015.01.005
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发表时间：
2015-02
期刊：
影响因子：
8.8
通讯作者：
Rikako Sanuki;Satoshi Watanabe;Yuko Sugita;Shoichi Irie;Takashi Kozuka;Mariko Shimada;S. Ueno;J. Usukura;T. Furukawa
中科院分区：
文献类型：
--
作者：
Rikako Sanuki;Satoshi Watanabe;Yuko Sugita;Shoichi Irie;Takashi Kozuka;Mariko Shimada;S. Ueno;J. Usukura;T. Furukawa
在脊椎动物视网膜发育中，视网膜神经元的轴突末梢在狭窄的固定区域内进行突触接触，并且这些位置此后被维持。然而，这些固定的突触位置的组织的机制和生物学逻辑知之甚少。我们在这里展示了一种膜支架蛋白，4.1G，在视网膜光感受器中高度表达，并且对于它们正确的突触位置的排列至关重要。1G缺乏的视网膜表现出感光末梢的错误定位，尽管它们的突触连接正常形成。4.1G蛋白结合的AP3B2蛋白，这是参与神经元膜贩运，促进神经突起的延伸，在AP3B2依赖的方式。4.1G突变小鼠表现出视动反应的视敏度障碍，这表明正确的突触位置是正常的视觉功能所必需的。总之，本研究中的数据提供了对神经回路形成中适当突触位置的机制和重要性的深入了解。
In vertebrate retinal development, the axonal terminals of retinal neurons make synaptic contacts within narrow fixed regions, and these locations are maintained thereafter. However, the mechanisms and biological logic of the organization of these fixed synapse locations are poorly understood. We show here that a membrane scaffold protein, 4.1G, is highly expressed in retinal photoreceptors and is essential for the arrangement of their correct synapse location. The4.1G-deficient retina exhibits mislocalization of photoreceptor terminals, although their synaptic connections are normally formed. The 4.1G protein binds to the AP3B2 protein, which is involved in neuronal membrane trafficking, and promotes neurite extension in an AP3B2-dependent manner.4.1Gmutant mice showed visual acuity impairments in an optokinetic response, suggesting that correct synapse location is required for normal visual function. Taken together, the data in this study provide insight into the mechanism and importance of proper synapse location in neural circuit formation.