LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

J Comp Neurol. 2021 Jan;529(1):221-233. doi: 10.1002/cne.24944. Epub 2020 Jun 27.


Leucine rich repeat transmembrane (LRRTM) proteins are synaptic adhesion molecules with roles in synapse formation and signaling. LRRTM4 transcripts were previously shown to be enriched in rod bipolar cells (BCs), secondary neurons of the retina that form synapses with rod photoreceptors. Using two different antibodies, LRRTM4 was found to reside primarily at rod BC dendritic tips, where it colocalized with the transduction channel protein, TRPM1. LRRTM4 was not detected at dendritic tips of ON-cone BCs. Following somatic knockout of LRRTM4 in BCs by subretinal injection and electroporation of CRISPR/Cas9, LRRTM4 was abolished or reduced in the dendritic tips of transfected cells. Knockout cells had a normal complement of TRPM1 at their dendritic tips, while GPR179 accumulation was partially reduced. In experiments with heterologously expressed protein, the extracellular domain of LRRTM4 was found to engage in heparan-sulfate dependent binding with pikachurin. These results implicate LRRTM4 in the GPR179-pikachurin-dystroglycan transsynaptic complex at rod synapses.

Keywords: LRRTM4; RRID: CVCL_0045; RRID: IMSR_CRL:22; RRID:AB_2138196; RRID:AB_2284227; RRID:AB_2336642; RRID:Addgene_18817; RRID:Addgene_59313; pikachurin; rod bipolar cell; rod photoreceptor; synaptic adhesion molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism*
  • Retinal Bipolar Cells / chemistry
  • Retinal Bipolar Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / chemistry
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Synapses / chemistry
  • Synapses / metabolism*


  • LRRTM4 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins