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

Cell Rep. 2018 Mar 27;22(13):3548-3561. 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.

Keywords: ON-bipolar cell; circuit; cone photoreceptor cell; retina; synapse formation; visual acuity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Receptors, Metabotropic Glutamate / metabolism
  • Retinal Bipolar Cells / metabolism
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Synapses / genetics
  • Synapses / metabolism
  • Visual Acuity / genetics
  • Visual Acuity / physiology*


  • Membrane Glycoproteins
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 6