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Proteomic screen reveals diverse protein transport between connected neurons in the visual system


ABSTRACT: Intercellular transfer of toxic proteins between neurons is thought to contribute to neurodegenerative disease, however whether direct inter-neuronal protein transfer occurs in the healthy brain is not clear. To assess the prevalence and identity of transferred proteins and the cellular specificity of transfer, we biotinylated retinal ganglion cell proteins in vivo and examined biotinylated proteins transported through the rodent visual circuit using microscopy, biochemistry, and mass spectrometry. Electron microscopy demonstrated preferential transfer of biotinylated proteins from retinogeniculate inputs to excitatory LGN neurons compared to GABAergic neurons. An unbiased mass spectrometry-based screen identified 200 transneuronally transported proteins (TNTPs) isolated from visual cortex. The majority of TNTPs are present in neuronal exosomes and virally-expressed TNTPs, including tau and synuclein, were detected in isolated exosomes and postsynaptic neurons. Our data demonstrate transfer of diverse endogenous proteins between neurons in the healthy intact brain and suggest that TNTP transport may be mediated by exosomes.

INSTRUMENT(S): LTQ Orbitrap, LTQ Orbitrap Elite

ORGANISM(S): Rattus Norvegicus (ncbitaxon:10116) Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Hollis T. Cline  

PROVIDER: MSV000088665 | MassIVE | Sun Jan 09 10:07:00 GMT 2022

REPOSITORIES: MassIVE

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