Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors 
in a trans-synaptic manner

Wang, Yuchen; Cao, Yan; Hays, Cassandra L.; Laboute, Thibaut; Ray, Thomas A.; Guerrero-Given, Debbie; Ahuja, Abhimanyu S.; Patil, Dipak; Rivero, Olga; Kamasawa, Naomi; Kay, Jeremy N.; Thoreson, Wallace B.; Martemyanov, Kirill A.

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Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner

Wang, Y., Cao, Y., Hays, C. L., Laboute, T., Ray, T. A., Guerrero-Given, D., et al. (2021). Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner. Proceedings of the National Academy of Sciences, (45). Retrieved from https://www.pnas.org/content/118/45/e2106694118.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-000C-DFBE-4 Versions-Permalink: https://hdl.handle.net/21.11116/0000-000C-DFBF-3

Genre: Zeitschriftenartikel

Alternativer Titel : Proceedings of the National Academy of Sciences

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Urheber:
Wang, Yuchen, Autor
Cao, Yan, Autor
Hays, Cassandra L., Autor
Laboute, Thibaut, Autor
Ray, Thomas A., Autor
Guerrero-Given, Debbie¹, Autor
Ahuja, Abhimanyu S., Autor
Patil, Dipak, Autor
Rivero, Olga, Autor
Kamasawa, Naomi¹, Autor
Kay, Jeremy N., Autor
Thoreson, Wallace B., Autor
Martemyanov, Kirill A., Autor

Affiliations:
1Max Planck Florida Institute for Neuroscience, Max Planck Society, One Max Planck Way, Jupiter FL 33458, USA, ou_1950288

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Schlagwörter: adhesion GPCR, horizontal cells, retina, synapses, vision

Zusammenfassung: Cone photoreceptors mediate daylight vision in vertebrates. Changes in neurotransmitter release at cone synapses encode visual information and is subject to precise control by negative feedback from enigmatic horizontal cells. However, the mechanisms that orchestrate this modulation are poorly understood due to a virtually unknown landscape of molecular players. Here, we report a molecular player operating selectively at cone synapses that modulates effects of horizontal cells on synaptic release. Using an unbiased proteomic screen, we identified an adhesion GPCR Latrophilin3 (LPHN3) in horizontal cell dendrites that engages in transsynaptic control of cones. We detected and characterized a prominent splice isoform of LPHN3 that excludes a element with inhibitory influence on transsynaptic interactions. A gain-of-function mouse model specifically routing LPHN3 splicing to this isoform but not knockout of LPHN3 diminished CaV1.4 calcium channel activity profoundly disrupted synaptic release by cones and resulted in synaptic transmission deficits. These findings offer molecular insight into horizontal cell modulation on cone synaptic function and more broadly demonstrate the importance of alternative splicing in adhesion GPCRs for their physiological function.