ERG responses to high-frequency flickers require FAT3 signaling in mouse retinal bipolar cells
Vision is initiated by the reception of light by photoreceptors and subsequent processing via downstream retinal neurons. Proper circuit organization depends on the multifunctional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here, we investigated the retinal function of Fat3 mutant mice and found decreases in both electroretinography and perceptual responses to high-frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. The role of FAT3 in the response to high temporal frequency flashes depends upon its ability to transduce an intracellular signal. Mechanistically, FAT3 binds to the synaptic protein PTPσ intracellularly and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. These findings expand the repertoire of FAT3's functions and reveal its importance in bipolar cells for high-frequency light response.
Authors
- Sean K. Wang (ORCID: https://orcid.org/0000-0003-1557-8510)
- Evelyn C. Avilés (ORCID: https://orcid.org/0000-0002-0448-487X)
- Yunlu Xue (ORCID: https://orcid.org/0000-0002-2088-9826)
- Lisa V. Goodrich (ORCID: https://orcid.org/0000-0002-3331-8600)
- Constance L. Cepko (ORCID: https://orcid.org/0000-0002-9945-6387)
- Shuxiang Shi (ORCID: https://orcid.org/0009-0009-3478-4353)
- Vladimir J. Kefalov (ORCID: https://orcid.org/0000-0002-1659-008X)
- Lucas Lin
- Sarina Patel (ORCID: https://orcid.org/0009-0004-2766-0663)
- Sebastian Cordero
Institutions
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Pontificia Universidad Católica de Chile (CL)
- University of California, Irvine (US)
- ShanghaiTech University (CN)
- Boston VA Research Institute (US)
Publication Details
- Journal
- The Journal of General Physiology
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1085/jgp.202413642
- Citations
- 5
- Primary Topic
- Retinal Development and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Howard Hughes Medical Institute
- Research to Prevent Blindness
- University of Southern California
- Vanderbilt University
- Washington University in St. Louis
- Cleveland Clinic
- Itä-Suomen Yliopisto
- International Brain Research Organization
- Université de Bordeaux
- Agencia Nacional de Investigación y Desarrollo
- National Institutes of Health
- University of California, Los Angeles
- University of California, Irvine