Evidence map›Paper›PMID 36624498›Full record

ArticleFluids and barriers of the CNS2023

Apicobasal transferrin receptor localization and trafficking in brain capillary endothelial cells.

Simone S E Nielsen, Mikkel R Holst, Kristine Langthaler, Sarah Christine Christensen, Elisabeth Helena Bruun, Birger Brodin, Morten S Nielsen

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Simone S E NielsenDepartment of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
Mikkel R HolstDepartment of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
Kristine LangthalerCNS Drug Delivery and Barrier Modelling, University of Copenhagen, Copenhagen, Denmark.
Sarah Christine ChristensenPathology & Imaging, Novo Nordisk, Måløv, Denmark.
Elisabeth Helena BruunDepartment of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
Birger BrodinDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Morten S NielsenDepartment of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark. mn@biomed.au.dk.
Aarhus University · DKLundbeck (Denmark) · DKNovo Nordisk (Denmark) · DKUniversity of Copenhagen · DK

Funding

Lundbeckfonden R155-2013-14113
6 · The paper itself

Abstract

The detailed mechanisms by which the transferrin receptor (TfR) and associated ligands traffic across brain capillary endothelial cells (BECs) of the CNS-protective blood-brain barrier constitute an important knowledge gap within maintenance and regulation of brain iron homeostasis. This knowledge gap also presents a major obstacle in research aiming to develop strategies for efficient receptor-mediated drug delivery to the brain. While TfR-mediated trafficking from blood to brain have been widely studied, investigation of TfR-mediated trafficking from brain to blood has been limited. In this study we investigated TfR distribution on the apical and basal plasma membranes of BECs using expansion microscopy, enabling sufficient resolution to separate the cellular plasma membranes of these morphological flat cells, and verifying both apical and basal TfR membrane domain localization. Using immunofluorescence-based transcellular transport studies, we delineated endosomal sorting of TfR endocytosed from the apical and basal membrane, respectively, as well as bi-directional TfR transcellular transport capability. The findings indicate different intracellular sorting mechanisms of TfR, depending on the apicobasal trafficking direction across the BBB, with the highest transcytosis capacity in the brain-to-blood direction. These results are of high importance for the current understanding of brain iron homeostasis. Also, the high level of TfR trafficking from the basal to apical membrane of BECs potentially explains the low transcytosis which are observed for the TfR-targeted therapeutics to the brain parenchyma.

Indexed as

BrainEndothelial CellsBlood-Brain BarrierIronReceptors, TransferrinIronReceptors, TransferrinApicobasal polarityBlood–brain barrierBrain drug deliveryBrain endothelial cellsExpansion microscopyIntracellular traffickingTransferrin receptor (TfR)

Identifiers

PMID36624498
PMCPMC9830855
OpenAlexW4313888444

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.