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TMT-coupled phosphoproteomics support novel role of TWEAK/Fn14 signaling in synaptic function

ABSTRACT: The study aims at illustrate novel role of TWEAK/Fn14 signaling in synapse function by combining electrophysiological and phosphoproteomic approaches. The results show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and post-synaptic proteins in adult mouse hippocampal slices. Two models featuring synaptic deficits were used in the study. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Ru Wei

LAB HEAD: Doug Johnson

PROVIDER: PXD021582 | Pride | 2021-02-02

REPOSITORIES: Pride

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	MaxQuantResult_20171109-032830.zip	Other
	QH2_171106_RG1_S_Fn14_TMTn1_frac1.raw	Raw
	QH2_171106_RG1_S_Fn14_TMTn1_frac2.raw	Raw
	QH2_171106_RG1_S_Fn14_TMTn1_frac3.raw	Raw
	QH2_171106_RG1_S_Fn14_TMTn1_frac4.raw	Raw

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