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A Novel Role for UNC119 as an Enhancer of Synaptic Transmission

Mammalian UNC119 is a ciliary trafficking chaperone highly expressed in the inner segment of retinal photoreceptors. Previous research has shown that UNC119 can bind to transducin, the synaptic ribbon protein RIBEYE, and the calcium-binding protein CaBP4, suggesting that UNC119 may have a role in sy...

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Autores principales: Fehlhaber, Katherine E., Majumder, Anurima, Boyd, Kimberly K., Griffis, Khris G., Artemyev, Nikolai O., Fain, Gordon L., Sampath, Alapakkam P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178850/
https://www.ncbi.nlm.nih.gov/pubmed/37175812
http://dx.doi.org/10.3390/ijms24098106
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author Fehlhaber, Katherine E.
Majumder, Anurima
Boyd, Kimberly K.
Griffis, Khris G.
Artemyev, Nikolai O.
Fain, Gordon L.
Sampath, Alapakkam P.
author_facet Fehlhaber, Katherine E.
Majumder, Anurima
Boyd, Kimberly K.
Griffis, Khris G.
Artemyev, Nikolai O.
Fain, Gordon L.
Sampath, Alapakkam P.
author_sort Fehlhaber, Katherine E.
collection PubMed
description Mammalian UNC119 is a ciliary trafficking chaperone highly expressed in the inner segment of retinal photoreceptors. Previous research has shown that UNC119 can bind to transducin, the synaptic ribbon protein RIBEYE, and the calcium-binding protein CaBP4, suggesting that UNC119 may have a role in synaptic transmission. We made patch-clamp recordings from retinal slices in mice with the UNC119 gene deleted and showed that removal of even one gene of UNC119 has no effect on the rod outer segment photocurrent, but acted on bipolar cells much like background light: it depolarized membrane potential, decreased sensitivity, accelerated response decay, and decreased the Hill coefficient of the response–intensity relationship. Similar effects were seen on rod bipolar-cell current and voltage responses, and after exposure to bright light to translocate transducin into the rod inner segment. These findings indicate that UNC119 deletion reduces the steady-state glutamate release rate at rod synapses, though no change in the voltage dependence of the synaptic Ca current was detected. We conclude that UNC119, either by itself or together with transducin, can facilitate the release of glutamate at rod synapses, probably by some interaction with RIBEYE or other synaptic proteins rather than by binding to CaBP4 or calcium channels.
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spelling pubmed-101788502023-05-13 A Novel Role for UNC119 as an Enhancer of Synaptic Transmission Fehlhaber, Katherine E. Majumder, Anurima Boyd, Kimberly K. Griffis, Khris G. Artemyev, Nikolai O. Fain, Gordon L. Sampath, Alapakkam P. Int J Mol Sci Article Mammalian UNC119 is a ciliary trafficking chaperone highly expressed in the inner segment of retinal photoreceptors. Previous research has shown that UNC119 can bind to transducin, the synaptic ribbon protein RIBEYE, and the calcium-binding protein CaBP4, suggesting that UNC119 may have a role in synaptic transmission. We made patch-clamp recordings from retinal slices in mice with the UNC119 gene deleted and showed that removal of even one gene of UNC119 has no effect on the rod outer segment photocurrent, but acted on bipolar cells much like background light: it depolarized membrane potential, decreased sensitivity, accelerated response decay, and decreased the Hill coefficient of the response–intensity relationship. Similar effects were seen on rod bipolar-cell current and voltage responses, and after exposure to bright light to translocate transducin into the rod inner segment. These findings indicate that UNC119 deletion reduces the steady-state glutamate release rate at rod synapses, though no change in the voltage dependence of the synaptic Ca current was detected. We conclude that UNC119, either by itself or together with transducin, can facilitate the release of glutamate at rod synapses, probably by some interaction with RIBEYE or other synaptic proteins rather than by binding to CaBP4 or calcium channels. MDPI 2023-04-30 /pmc/articles/PMC10178850/ /pubmed/37175812 http://dx.doi.org/10.3390/ijms24098106 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fehlhaber, Katherine E.
Majumder, Anurima
Boyd, Kimberly K.
Griffis, Khris G.
Artemyev, Nikolai O.
Fain, Gordon L.
Sampath, Alapakkam P.
A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title_full A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title_fullStr A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title_full_unstemmed A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title_short A Novel Role for UNC119 as an Enhancer of Synaptic Transmission
title_sort novel role for unc119 as an enhancer of synaptic transmission
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178850/
https://www.ncbi.nlm.nih.gov/pubmed/37175812
http://dx.doi.org/10.3390/ijms24098106
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