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Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma

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Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. / Grapp, Marcel; Wrede, Arne; Schweizer, Michaela; Hüwel, Sabine; Galla, Hans-Joachim; Snaidero, Nicolas; Simons, Mikael; Bückers, Johanna; Low, Philip S; Urlaub, Henning; Gärtner, Jutta; Steinfeld, Robert.

in: NAT COMMUN, Jahrgang 4, 01.01.2013, S. 2123.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Grapp, M, Wrede, A, Schweizer, M, Hüwel, S, Galla, H-J, Snaidero, N, Simons, M, Bückers, J, Low, PS, Urlaub, H, Gärtner, J & Steinfeld, R 2013, 'Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma', NAT COMMUN, Jg. 4, S. 2123. https://doi.org/10.1038/ncomms3123

APA

Grapp, M., Wrede, A., Schweizer, M., Hüwel, S., Galla, H-J., Snaidero, N., Simons, M., Bückers, J., Low, P. S., Urlaub, H., Gärtner, J., & Steinfeld, R. (2013). Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. NAT COMMUN, 4, 2123. https://doi.org/10.1038/ncomms3123

Vancouver

Grapp M, Wrede A, Schweizer M, Hüwel S, Galla H-J, Snaidero N et al. Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. NAT COMMUN. 2013 Jan 1;4:2123. https://doi.org/10.1038/ncomms3123

Bibtex

@article{e629aeb481574cd5ab62f978b8ec2dac,
title = "Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma",
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.",
keywords = "Adolescent, Adult, Animals, Cell Polarity, Child, Choroid Plexus, Cytoplasmic Vesicles, Dogs, Exosomes, Female, Folate Receptor 1, Folic Acid, Humans, Madin Darby Canine Kidney Cells, Male, Mice, Models, Biological, Monensin, Protein Transport, Proton-Coupled Folate Transporter, Rats, Tetrahydrofolates, Transcytosis, Transferrin, Young Adult",
author = "Marcel Grapp and Arne Wrede and Michaela Schweizer and Sabine H{\"u}wel and Hans-Joachim Galla and Nicolas Snaidero and Mikael Simons and Johanna B{\"u}ckers and Low, {Philip S} and Henning Urlaub and Jutta G{\"a}rtner and Robert Steinfeld",
year = "2013",
month = jan,
day = "1",
doi = "10.1038/ncomms3123",
language = "English",
volume = "4",
pages = "2123",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma

AU - Grapp, Marcel

AU - Wrede, Arne

AU - Schweizer, Michaela

AU - Hüwel, Sabine

AU - Galla, Hans-Joachim

AU - Snaidero, Nicolas

AU - Simons, Mikael

AU - Bückers, Johanna

AU - Low, Philip S

AU - Urlaub, Henning

AU - Gärtner, Jutta

AU - Steinfeld, Robert

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Animals

KW - Cell Polarity

KW - Child

KW - Choroid Plexus

KW - Cytoplasmic Vesicles

KW - Dogs

KW - Exosomes

KW - Female

KW - Folate Receptor 1

KW - Folic Acid

KW - Humans

KW - Madin Darby Canine Kidney Cells

KW - Male

KW - Mice

KW - Models, Biological

KW - Monensin

KW - Protein Transport

KW - Proton-Coupled Folate Transporter

KW - Rats

KW - Tetrahydrofolates

KW - Transcytosis

KW - Transferrin

KW - Young Adult

U2 - 10.1038/ncomms3123

DO - 10.1038/ncomms3123

M3 - SCORING: Journal article

C2 - 23828504

VL - 4

SP - 2123

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -