Journal
CELL REPORTS
Volume 25, Issue 1, Pages 130-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.08.068
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Funding
- NIH [EY018139, EY028033, MH105482]
- European Research Council (ERC) [311083]
- Fonds voor Wetenschappelijk Onderzoek (FWO) Odysseus Grant
- Japan Society for the Promotion of Science (JSPS) [18H02593, 16K08583]
- Grants-in-Aid for Scientific Research [16K08583] Funding Source: KAKEN
- European Research Council (ERC) [311083] Funding Source: European Research Council (ERC)
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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 presynaptic dystroglycan glycoprotein complex. We further demonstrate that this transsynaptic assembly plays an essential role in synaptic transmission of photoreceptor signals.
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