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Verfasst von:Bortfeld, Miriam [VerfasserIn]   i
 Rius, Maria [VerfasserIn]   i
 König, Jörg [VerfasserIn]   i
 Herold-Mende, Christel [VerfasserIn]   i
 Keppler, Dietrich [VerfasserIn]   i
Titel:Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system
Verf.angabe:M. Bortfeld, M. Rius, J. König, C. Herold-Mende, A.T. Nies and D. Keppler
Jahr:2006
Jahr des Originals:2005
Umfang:11 S.
Fussnoten:Available online 15 December 2005 ; Gesehen am 18.02.2021
Titel Quelle:Enthalten in: Neuroscience
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1976
Jahr Quelle:2006
Band/Heft Quelle:137(2006), 4, Seite 1247-1257
ISSN Quelle:1873-7544
Abstract:Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 μM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.
DOI:doi:10.1016/j.neuroscience.2005.10.025
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.neuroscience.2005.10.025
 Volltext: https://www.sciencedirect.com/science/article/pii/S0306452205011565
 DOI: https://doi.org/10.1016/j.neuroscience.2005.10.025
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:dehydroepiandrosterone 3-sulfate
 GABA receptor modulation
 gliomas
 multidrug resistance proteins
 neurosteroids
 paroxysmal kinesigenic choreoathetosis
K10plus-PPN:1748650882
Verknüpfungen:→ Zeitschrift

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