Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity

• Published in: Cell reports (Cambridge) 2018-03, Vol.22 (13), p.3548-3561
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: circuit; cone photoreceptor cell; ON-bipolar cell; retina; synapse formation; visual acuity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.03.007

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. [Display omitted] •Lrit1-deficient mice exhibit aberrant morphology of cone photoreceptor pedicles•Lrit1 loss delays signal transmission from cone photoreceptors to cone bipolars•Lrit1 interacts with postsynaptic mGluR6 and presynaptic Frmpd2 scaffold protein•Lrit1 is required for the development of accurate visual function in mice Ueno et al. finds that Lrit1 plays an important role in regulating the synaptic connection between cone photoreceptors and cone ON-bipolar cells. The Frmpd2-Lrit1-mGluR6 axis is crucial for selective synapse formation in cone photoreceptors and for development of normal visual function.