RRC ID 54173
Author Orlandi C, Omori Y, Wang Y, Cao Y, Ueno A, Roux MJ, Condomitti G, de Wit J, Kanagawa M, Furukawa T, Martemyanov KA.
Title Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors.
Journal Cell Rep
Abstract 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.
Volume 25(1)
Pages 130-145.e5
Published 2018-10-2
DOI 10.1016/j.celrep.2018.08.068
PII S2211-1247(18)31372-X
PMID 30282023
PMC PMC6203450
MeSH Animals Carrier Proteins / metabolism* Dystroglycans / metabolism* Extracellular Matrix / metabolism HEK293 Cells Humans Mice Mice, Knockout Nerve Tissue Proteins / metabolism* Photoreceptor Cells / metabolism* Protein Binding Receptors, G-Protein-Coupled / metabolism* Synapses / metabolism Synaptic Transmission / physiology
IF 8.109
Times Cited 13
Mice RBRC05552