Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity
Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity
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Lrit1 是一种视网膜跨膜蛋白，调节视锥细胞中的选择性突触形成和视力
DOI：
10.1016/j.celrep.2018.03.007
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Furukawa Takahisa
中科院分区：
文献类型：
--
作者：
Ueno Akiko;Omori Yoshihiro;Sugita Yuko;Watanabe Satoshi;Chaya Taro;Kozuka Takashi;Kon Tetsuo;Yoshida Satoyo;Matsushita Kenji;Kuwahara Ryusuke;Kajimura Naoko;Okada Yasushi;Furukawa Takahisa
在脊椎动物的视网膜中，视锥感光细胞通过将光诱发信号传递到双极细胞和/或双极细胞，在明视视觉中起着关键作用。然而，视锥感光细胞通路中选择性突触形成的机制仍然知之甚少。在这里，我们发现Lrit1是一种富含亮氨酸的跨膜蛋白，定位于光感受器突触终末，调节视锥感光细胞和视锥双极细胞之间的突触连接。Lrit1缺乏的视网膜表现出视锥感光器蒂的异常形态，以及视锥感光细胞到视锥双极细胞的信号传递障碍。此外，我们证明了Lrit1与光感受器支架蛋白Frmpd2和双极细胞特异性谷氨酸受体mGluR6相互作用。此外，Lrit1基因缺失的小鼠在其视动反应中显示出视力受损。这些结果表明，Frmpd2-Lrit1-mGluR6轴调节视锥感受器选择性突触的形成，对正常的视觉功能是必不可少的。
In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells.Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally,Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function.