Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation.
Action Potentials
/ genetics
Amacrine Cells
/ metabolism
Animals
Animals, Newborn
/ genetics
Calcium Signaling
/ genetics
Embryonic Development
/ genetics
Gene Expression Regulation, Developmental
/ genetics
Patch-Clamp Techniques
Phosphorylation
Protein Binding
Retina
/ growth & development
Retinal Ganglion Cells
/ metabolism
Synaptic Potentials
/ genetics
Synaptosomal-Associated Protein 25
/ genetics
Visual Pathways
/ physiology
PKA-mediated phosphorylation
SNAP-25
retinal waves
retinogeniculate projection
starburst amacrine cells
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
19 02 2019
19 02 2019
Historique:
pubmed:
8
2
2019
medline:
2
5
2019
entrez:
8
2
2019
Statut:
ppublish
Résumé
Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.
Identifiants
pubmed: 30728295
pii: 1812169116
doi: 10.1073/pnas.1812169116
pmc: PMC6386712
doi:
Substances chimiques
Snap25 protein, mouse
0
Synaptosomal-Associated Protein 25
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3262-3267Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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