Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier

Laura Wu, A. G Miriam Leenders, Sharon Cooperman, Esther Meyron-Holtz, Sophia Smith, William Land, Robert Y L Tsai, Urs V. Berger, Zu Hang Sheng, Tracey A. Rouault

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Iron homeostasis in the mammalian brain is an important and poorly understood subject. Transferrin-bound iron enters the endothelial cells of the blood-brain barrier from the systemic circulation, and iron subsequently dissociates from transferrin to enter brain parenchyma by an unknown mechanism. In recent years, several iron transporters, including the iron importer DMT1 (Ireg1, MTP, DCT1) and the iron exporter ferroportin (SLC11A3, Ireg, MTP1) have been cloned and characterized. To better understand brain iron homeostasis, we have characterized the distribution of ferroportin, the presumed intestinal iron exporter, and have evaluated its potential role in regulation of iron homeostasis in the central nervous system. We discovered using in situ hybridization and immunohistochemistry that ferroportin is expressed in the endothelial cells of the blood-brain barrier, in neurons, oligodendrocytes, astrocytes, and the choroid plexus and ependymal cells. In addition, we discovered using techniques of immunoelectron microscopy and biochemical purification of synaptic vesicles that ferroportin is associated with synaptic vesicles. In the blood-brain barrier, it is likely that ferroportin serves as a molecular transporter of iron on the abluminal membrane of polarized endothelial cells. The role of ferroportin in synaptic vesicles is unknown, but its presence at that site may prove to be of great importance in neuronal iron toxicity. The widespread representation of ferroportin at sites such as the blood-brain barrier and synaptic vesicles raises the possibility that trafficking of elemental iron may be instrumental in the distribution of iron in the central nervous system.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalBrain Research
Volume1001
Issue number1-2
DOIs
StatePublished - Mar 19 2004
Externally publishedYes

Fingerprint

Synaptic Vesicles
Blood-Brain Barrier
Iron
Homeostasis
Endothelial Cells
Transferrin
metal transporting protein 1
Brain
Central Nervous System
Choroid Plexus
Immunoelectron Microscopy
Oligodendroglia
Astrocytes
In Situ Hybridization
Immunohistochemistry

Keywords

  • Endothelial transport
  • Iron transport
  • Neurodegeneration
  • Synaptic vesicles

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

Cite this

Wu, L., Leenders, A. G. M., Cooperman, S., Meyron-Holtz, E., Smith, S., Land, W., ... Rouault, T. A. (2004). Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. Brain Research, 1001(1-2), 108-117. https://doi.org/10.1016/j.brainres.2003.10.066

Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. / Wu, Laura; Leenders, A. G Miriam; Cooperman, Sharon; Meyron-Holtz, Esther; Smith, Sophia; Land, William; Tsai, Robert Y L; Berger, Urs V.; Sheng, Zu Hang; Rouault, Tracey A.

In: Brain Research, Vol. 1001, No. 1-2, 19.03.2004, p. 108-117.

Research output: Contribution to journalArticle

Wu, L, Leenders, AGM, Cooperman, S, Meyron-Holtz, E, Smith, S, Land, W, Tsai, RYL, Berger, UV, Sheng, ZH & Rouault, TA 2004, 'Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier', Brain Research, vol. 1001, no. 1-2, pp. 108-117. https://doi.org/10.1016/j.brainres.2003.10.066
Wu, Laura ; Leenders, A. G Miriam ; Cooperman, Sharon ; Meyron-Holtz, Esther ; Smith, Sophia ; Land, William ; Tsai, Robert Y L ; Berger, Urs V. ; Sheng, Zu Hang ; Rouault, Tracey A. / Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. In: Brain Research. 2004 ; Vol. 1001, No. 1-2. pp. 108-117.
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