Active zone protein CAST is a component of conventional and ribbon synapses in mouse retina

Fast neurotransmitter release from ribbon synapses via Ca2+-triggered exocytosis requires tight coupling of L-type Ca2+channels to release-ready synaptic vesicles at the presynaptic active zone, which is localized at the base of the ribbon. Here, we used genetic, electrophysiological, and ultrastructural analyses to probe the architecture of ribbon synapses by perturbing the function of RIM-binding proteins (RBPs) as central active-zone scaffolding molecules. We found that genetic deletion of RBP1 and RBP2 did not impair synapse ultrastructure of ribbon-type synapses formed between rod bipolar cells (RBCs) and amacrine type-2 (AII) cells in the mouse retina but dramatically reduced the density of presynaptic Ca2+channels, decreased and desynchronized evoked neurotransmitter release, and rendered evoked and spontaneous neurotransmitter release sensitive to the slow Ca2+buffer EGTA. These findings suggest that RBPs tether L-type Ca2+channels to the active zones of ribbon synapses, thereby synchronizing vesicle exocytosis and promoting high-fidelity information transfer in retinal circuits.

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Early steps in the assembly of photoreceptor ribbon synapses in the mouse retina: The involvement of precursor spheres

The Journal of Comparative Neurology ◽

10.1002/cne.21915 ◽

2009 ◽

Vol 512 (6) ◽

pp. 814-824 ◽

Cited By ~ 64

Author(s):

Hanna Regus-Leidig ◽

Susanne tom Dieck ◽

Dana Specht ◽

Lars Meyer ◽

Johann Helmut Brandstätter

Keyword(s):

Mouse Retina ◽

Ribbon Synapses

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Rab3 Proteins and SNAP-25, Essential Components of the Exocytosis Machinery in Conventional Synapses, are Absent from Ribbon Synapses of the Mouse Retina

European Journal of Neuroscience ◽

10.1111/j.1460-9568.1996.tb01177.x ◽

1996 ◽

Vol 8 (1) ◽

pp. 162-168 ◽

Cited By ~ 36

Author(s):

D. Grabs ◽

M. Bergmann ◽

M. Urban ◽

A. Post ◽

M. Gratzl

Keyword(s):

Mouse Retina ◽

Ribbon Synapses ◽

Essential Components

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Site-specific gains and losses of heterochromatin accelerate the age-related neurodegeneration through the cascading destruction of KDM3B-centered epigenomic network

10.21203/rs.3.rs-1246914/v1 ◽

2022 ◽

Author(s):

Mi-Jin An ◽

Ji-Young Kim ◽

Jinhong Park ◽

Jinho Kim ◽

Dae-Hyun Kim ◽

...

Keyword(s):

Transcriptome Profiling ◽

Mouse Retina ◽

Sequencing Analysis ◽

Epigenetic Alterations ◽

Ribbon Synapses ◽

Age Related ◽

Retinal Neurodegeneration ◽

Apoptotic Genes ◽

Gains And Losses ◽

Universal Mechanism

Abstract Epigenetic alterations explained by the “loss of heterochromatin” model have been proposed as a universal mechanism of aging, but the region-specific changes of heterochromatin during aging are unclear. Here, we examine age-dependent transcriptomic profiling of mouse retinal neurons to identify epigenetic regulators involved in heterochromatin loss. RNA sequencing analysis revealed gradual down-regulation of Kdm3b during retinal aging. Disruption of Kdm3b (Kdm3b+/-) in 12-month-old mouse retina decreased the number of cone photoreceptors and changed the morphology of cone ribbon synapses. Integration of transcriptome profiling with epigenomic analysis demonstrated gain of heterochromatin feature in synapse assembly and vesicle transport genes via the accumulation of H3K9 mono- and di-methylation. However, the loss of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that this KDM3B-centered epigenomic network is crucial for maintaining cone photoreceptor homeostasis via the modulation of gene-set specific heterochromatin features during aging.

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