In epithelia, the glutamate transporter EAAC1/EAAT3 mediates the absorption of dicarboxylic amino acids and has been involved in dicarboxylic aminoaciduria, a rare disease in which glutamate and aspartate accumulate in urine. EAAC1 cell-surface distribution is regulated by interaction with accessory proteins, which remain to be identified. By means of yeast two hybrid system, we identified the PDZ domain containing protein 1 (PDZK1), an adaptor protein involved in the apical domain organization of epithelia. The interaction was confirmed by affinity chromatography and co-immunoprecipitation experiments. Immunostaining of pig jejunum with antisera against PDZK1 and EAAC1 revealed co-localization between the two proteins in the apical domain of enterocytes and in sub-apical vesicular compartments. PDZK1 not only co-localized but also functionally interacted with the transporter, because its presence increased the glutamate uptake in MDCK cells expressing wild type EAAC1, but not a mutant transporter lacking the PDZ interaction sequence. Taken together, these results demonstrate that PDZK1 functionally interacts with EAAC1 and modulates its cell-surface activity.

The adaptor protein PDZK1/NHERF3 interacts with the glutamate transporter EAAC1 and controls its surface activity in epithelial cells / S. Sala, E.S. Di Cairano, G. Fantin, V.F. Sacchi, N. Anzai, C. Perego. - In: ACTA PHYSIOLOGICA. - ISSN 1748-1708. - 200:supplement 681(2010), pp. P31-P31. ((Intervento presentato al 61. convegno National congress of the Italian physiological society tenutosi a Varese nel 2010.

The adaptor protein PDZK1/NHERF3 interacts with the glutamate transporter EAAC1 and controls its surface activity in epithelial cells

E.S. Di Cairano;V.F. Sacchi;C. Perego
2010

Abstract

In epithelia, the glutamate transporter EAAC1/EAAT3 mediates the absorption of dicarboxylic amino acids and has been involved in dicarboxylic aminoaciduria, a rare disease in which glutamate and aspartate accumulate in urine. EAAC1 cell-surface distribution is regulated by interaction with accessory proteins, which remain to be identified. By means of yeast two hybrid system, we identified the PDZ domain containing protein 1 (PDZK1), an adaptor protein involved in the apical domain organization of epithelia. The interaction was confirmed by affinity chromatography and co-immunoprecipitation experiments. Immunostaining of pig jejunum with antisera against PDZK1 and EAAC1 revealed co-localization between the two proteins in the apical domain of enterocytes and in sub-apical vesicular compartments. PDZK1 not only co-localized but also functionally interacted with the transporter, because its presence increased the glutamate uptake in MDCK cells expressing wild type EAAC1, but not a mutant transporter lacking the PDZ interaction sequence. Taken together, these results demonstrate that PDZK1 functionally interacts with EAAC1 and modulates its cell-surface activity.
glutamate transporter; epithelia; PDZ protein; PDZK1/NHERF3
Settore BIO/09 - Fisiologia
http://www.blackwellpublishing.com/aphmeeting/abstract.asp?MeetingID=772&id=86283
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/161022
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