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LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells
Author(s) -
Agosto Melina A.,
Wensel Theodore G.
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.24944
Subject(s) - biology , microbiology and biotechnology , electroporation , transmembrane protein , hek 293 cells , synapse , retina , extracellular , transmembrane domain , neuroscience , receptor , biochemistry , gene
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.