Intercellular transfer of toxic proteins between neurons is thought to contribute to neurodegenerative disease, but whether direct interneuronal 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, researchers from The Scripps Research Institute 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 lateral geniculate nucleus (LGN) neurons compared with GABAergic neurons. An unbiased mass spectrometry-based screen identified ∼200 transneuronally transported proteins (TNTPs) isolated from the visual cortex. The majority of TNTPs are present in neuronal exosomes, and virally expressed TNTPs, including tau and β-synuclein, were detected in isolated exosomes and postsynaptic neurons. These data demonstrate transfer of diverse endogenous proteins between neurons in the healthy intact brain and suggest that TNTP transport may be mediated by exosomes.
Proteomic screen reveals diverse protein transport between connected neurons in the visual system
Schiapparelli LM, Sharma P, He HY, Li J, Shah SH, McClatchy DB, Ma Y, Liu HH, Goldberg JL, Yates III JR, Cline HT. (2022) Proteomic screen reveals diverse protein transport between connected neurons in the visual system. Cell Rep 38(4), 110287. [article]