Publication: Agosto Lab

Trans-synaptic Interaction with mGluR6 Contributes to ELFN1 Presynaptic Enrichment in Rod Photoreceptors

Jaeeun Lee, Robyn V. McGowan and Melina A. Agosto

Link: doi.org/10.1523/JNEUROSCI.0785-25.2025

Published: Oct 22, 2025 Journal of Neuroscience, 45 (43) e0785252025

Abstract: At the glutamatergic synapses between rod photoreceptors and ON-type bipolar cells (BCs), neurotransmitter is detected by the postsynaptic metabotropic glutamate receptor mGluR6. This receptor forms trans-synaptic interactions with ELFN1, a presynaptic cell adhesion molecule expressed in rods, and ELFN1 is important for mGluR6 localization at BC dendritic tips. Here, we show that in mice of either sex lacking mGluR6, the presynaptic localization of ELFN1 is disrupted. In rods of mGluR6 null mice, ELFN1 is still restricted to the axon terminal spherules but is only partially colocalized with synapses. The ELFN1 localization defect is rescued by expressing mGluR6-EGFP in ON-BCs. In vitro binding experiments demonstrated that the leucine-rich repeat (LRR) and LRR C-terminal cap (LRRCT) regions of the ELFN1 extracellular domain (ECD) are necessary and sufficient for binding to all of the Group 3 mGluRs, including mGluR6. ELFN1-flag expressed in rods of wild-type mice is correctly localized at presynapses, colocalizing with the postsynaptic marker TRPM1 in the outer plexiform layer. Deletion of the LRRCT domain abolished trafficking of ELFN1-flag to rod spherules, whereas deletion of other parts of the ELFN1 ECD did not prevent axonal trafficking or correct presynaptic localization. Our results demonstrate bidirectional mutual regulation of presynaptic enrichment of ELFN1 and postsynaptic enrichment of mGluR6 at photoreceptor synapses.