Phosphorylation of cysteine string protein-α in starburst amacrine cells modulates gene expression in the developing rat retina
Date Issued
2016
Date
2016
Author(s)
Wo, Ting-Yu
Abstract
Prior to sensory experience, patterned spontaneous activity (termed retinal waves in the developing visual system) is essential for establishing functional neural circuits. In rodents, retinal waves during the first postnatal week up-regulate the expression of innate immune proteins, such as histocompatibility complex class I (MHCI), leading to synaptic refinement and eye-specific segregation of retinogeniculate projection. These waves are initiated by presynaptic starburst amacrine cells (SACs) releasing neurotransmitters to neighboring SACs or retinal ganglion cells (RGCs), displaying unique spatial and temporal patterns, with wave-like propagation of correlated firings and Ca2+ transients in the RGC layer. However, which pattern (spatial or temporal) of retinal waves is important for this activity-dependent gene expression remains unknown. We previously found that phosphorylation of cysteine string protein-α (CSPα) in presynaptic cells increases neurotransmitter release and wave frequency, without altering the spatial correlation of retinal waves. Thus, the effects by altering the CSPα phosphorylated state in wave-initiating cells can reflect how the wave temporal pattern regulates activity-dependent gene expression. In this study, we determine how the temporal pattern of retinal waves regulates activity-dependent gene expression in the developing rat retina. By utilizing the cell type-specific molecular perturbation, we found that overexpression of wild-type CSPα in SACs increased the expression of innate immune proteins compared to control, but overexpression of the CSPα phosphodeficient mutant (CSPα-S10A) in SACs did not. In addition, CSP-WT in SACs also increased the expression of the upstream transcription factor, pCREB, in postsynaptic cells compared to control or CSPα-S10A. Therefore, through increasing wave frequency, phosphorylation of CSPα in SACs regulates the retinal expression of innate immune genes. These results suggest that the temporal pattern of retinal waves is important for activity-dependent gene expression in the developing rat retina.
Subjects
Retinal waves
Starburst amacrine cells
Cysteine string protein
Innate immune genes
Retinal ganglion cells
Histocompatibility complex class I
Type
thesis
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