Abstract
SUMMARYEstablishing 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 uniquephysiological propertiesofindividual 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 oftheheparansulfateproteoglycan (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 presynaptic dystroglycan glycoprotein complex. We further demonstrate that this transsynaptic assembly plays an essential role in synaptic transmission of photoreceptor signals.
Highlights
Precise synaptic connectivity is one of the defining properties of the CNS
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
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
Summary
Precise synaptic connectivity is one of the defining properties of the CNS. The ability of neurons to form synapses with an extremely defined spatial and temporal resolution is essential to establish functional neuronal circuits, but the molecular mechanisms involved in neuronal wiring specificity are still poorly understood. Emerging proteomic studies increasingly point to their involvement in transsynaptic macromolecular complexes and interactions with ECM components (Bolliger et al, 2011; Cao et al, 2015; Kakegawa et al, 2015; Lanoue et al, 2013; Luo et al, 2011; O’Sullivan et al, 2012). Such effects were primarily shown for the subfamily of ‘‘adhesion’’ receptors, and the scope of this involvement and extent of conservation across the GPCR superfamily are yet to be explored
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