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

Publication ,  Journal Article
Wang, Y; Cao, Y; Hays, CL; Laboute, T; Ray, TA; Guerrero-Given, D; Ahuja, AS; Patil, D; Rivero, O; Kamasawa, N; Kay, JN; Thoreson, WB; Martemyanov, KA
Published in: Proc Natl Acad Sci U S A
November 9, 2021

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 9, 2021

Volume

118

Issue

45

Location

United States

Related Subject Headings

  • Synapses
  • Retinal Cone Photoreceptor Cells
  • Receptors, Peptide
  • Receptors, G-Protein-Coupled
  • Proteome
  • Protein Isoforms
  • Mice, Knockout
  • Mice
  • Calcium Channels
  • Animals
 

Citation

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Wang, Y., Cao, Y., Hays, C. L., Laboute, T., Ray, T. A., Guerrero-Given, D., … Martemyanov, K. A. (2021). Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner. Proc Natl Acad Sci U S A, 118(45). https://doi.org/10.1073/pnas.2106694118
Wang, Yuchen, Yan Cao, Cassandra L. Hays, Thibaut Laboute, Thomas A. Ray, Debbie Guerrero-Given, Abhimanyu S. Ahuja, et al. “Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner.Proc Natl Acad Sci U S A 118, no. 45 (November 9, 2021). https://doi.org/10.1073/pnas.2106694118.
Wang Y, Cao Y, Hays CL, Laboute T, Ray TA, Guerrero-Given D, et al. Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45).
Wang, Yuchen, et al. “Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner.Proc Natl Acad Sci U S A, vol. 118, no. 45, Nov. 2021. Pubmed, doi:10.1073/pnas.2106694118.
Wang Y, Cao Y, Hays CL, Laboute T, Ray TA, Guerrero-Given D, Ahuja AS, Patil D, Rivero O, Kamasawa N, Kay JN, Thoreson WB, Martemyanov KA. Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45).
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 9, 2021

Volume

118

Issue

45

Location

United States

Related Subject Headings

  • Synapses
  • Retinal Cone Photoreceptor Cells
  • Receptors, Peptide
  • Receptors, G-Protein-Coupled
  • Proteome
  • Protein Isoforms
  • Mice, Knockout
  • Mice
  • Calcium Channels
  • Animals