Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors

Abstract

Summary: Establishing synaptic contacts between neurons is paramount for nervous system function. This process involves transsynaptic interactions between a host of cell adhesion molecules that act in cooperation with the proteins of the extracellular matrix to specify unique physiological properties of individual synaptic connections. However, understanding of the molecular mechanisms that generate functional diversity in an input-specific fashion is limited. In this study, we identify that major components of the extracellular matrix proteins present in the synaptic cleft—members of the heparan sulfate proteoglycan (HSPG) family—associate with the GPR158/179 group of orphan receptors. Using the mammalian retina as a model system, we demonstrate that the HSPG member Pikachurin, released by photoreceptors, recruits a key post-synaptic signaling complex of downstream ON-bipolar neurons in coordination with the pre-synaptic dystroglycan glycoprotein complex. We further demonstrate that this transsynaptic assembly plays an essential role in synaptic transmission of photoreceptor signals. : Orlandi et al. identify transsynaptic assembly at photoreceptor synapses involving pre-synaptic dystrophin-dystroglycan complex and the post-synaptic orphan receptor GPR179 bridged by HSPG protein Pikachurin in the cleft and demonstrate its role in shaping transmission of photoreceptor signals. Keywords: synaptic specificity, heparan sulfate proteoglycan, HSPG, orphan receptor, ON-bipolar cells, retina, vision, synaptic transmission, transsynaptic interactions, ribbon synapse