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Journal Article

Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma.

MPS-Authors
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Bückers,  J.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1819279.pdf
(Publisher version), 5MB

Supplementary Material (public)

1819279_Supplement_1.pdf
(Supplementary material), 717KB

Citation

Grapp, M., Wrede, A., Schweizer, M., Hüwel, S., Galla, H., Snaidero, N., et al. (2013). Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nature Communications, 4: 2123. doi:10.1038/ncomms3123.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-164F-1
Abstract
Loss of folate receptor-α function is associated with cerebral folate transport deficiency and childhood-onset neurodegeneration. To clarify the mechanism of cerebral folate transport at the blood–cerebrospinal fluid barrier, we investigate the transport of 5-methyltetrahydrofolate in polarized cells. Here we identify folate receptor-α-positive intralumenal vesicles within multivesicular bodies and demonstrate the directional cotransport of human folate receptor-α, and labelled folate from the basolateral to the apical membrane in rat choroid plexus cells. Both the apical medium of folate receptor-α-transfected rat choroid plexus cells and human cerebrospinal fluid contain folate receptor-α-positive exosomes. Loss of folate receptor-α-expressing cerebrospinal fluid exosomes correlates with severely reduced 5-methyltetrahydrofolate concentration, corroborating the importance of the folate receptor-α-mediated folate transport in the cerebrospinal fluid. Intraventricular injections of folate receptor-α-positive and -negative exosomes into mouse brains demonstrate folate receptor-α-dependent delivery of exosomes into the brain parenchyma. Our results unravel a new pathway of folate receptor-α-dependent exosome-mediated folate delivery into the brain parenchyma and opens new avenues for cerebral drug targeting.