PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3

Olga Fedorenko, Cai Tang, Mentor Sopjani, Michael Föller, Eva Maria Gehring, Nathalie Strutz-Seebohm, Oana N. Ureche, Svetlana Ivanova, Arkadij Semke, Florian Lang, Guiscard Seebohm, Undine E. Lang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Introduction: According to previous observations, the gene encoding the phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) is associated with schizophrenia. Specifically, the mutation N251SPIP5K2A has been discovered in schizophrenic patients but not in healthy individuals. A defect of the excitatory amino acid transporter EAAT3 has similarly been implicated in the development of schizophrenia. The present study thus explored whether PIP5K2A is involved in the regulation of EAAT3 activity. Materials and methods: EAAT3 was expressed in Xenopus oocytes either without or with PIP5K2A, and EAAT3 transporter activity was estimated from the glutamate (2-mM)-induced current (Iglu) in dual electrode voltage clamp experiments. EAAT3 protein abundance in the cell membrane was estimated by Western blotting and confocal microscopy. Results: In EAAT3-expressing oocytes, Iglu was enhanced by coexpression of wild type PIP5K2A. Coexpression of the schizophrenia- associated mutant N251SPIP5K2A significantly decreased I glu in oocytes expressing EAAT3 with or without additional expression of wild type PIP5K2A. Thus, N251SPIP5K2A exerts a dominant inhibitory effect. Discussion: Membrane abundance of EAAT3 was increased by wild type PIP5K2A and decreased by N251SPIP5K2A in both EAAT3-expressing oocytes and human embryonic kidney cells. The present observations disclose a novel mechanism of EAAT3 regulation, which may contribute to the deranged regulation of excitability in schizophrenic patients.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalPsychopharmacology
Volume206
Issue number3
DOIs
Publication statusPublished - 31 Jul 2009

Fingerprint

Amino Acid Transport Systems
Excitatory Amino Acids
Oocytes
Schizophrenia
Xenopus
Confocal Microscopy
Glutamic Acid
Electrodes
Western Blotting
Cell Membrane
Kidney
Mutation
Membranes
Genes
Proteins

Keywords

  • Glutamate
  • Mutation
  • Neuroexcitability
  • PIP
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Fedorenko, O., Tang, C., Sopjani, M., Föller, M., Gehring, E. M., Strutz-Seebohm, N., ... Lang, U. E. (2009). PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. Psychopharmacology, 206(3), 429-435. https://doi.org/10.1007/s00213-009-1621-5

PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. / Fedorenko, Olga; Tang, Cai; Sopjani, Mentor; Föller, Michael; Gehring, Eva Maria; Strutz-Seebohm, Nathalie; Ureche, Oana N.; Ivanova, Svetlana; Semke, Arkadij; Lang, Florian; Seebohm, Guiscard; Lang, Undine E.

In: Psychopharmacology, Vol. 206, No. 3, 31.07.2009, p. 429-435.

Research output: Contribution to journalArticle

Fedorenko, O, Tang, C, Sopjani, M, Föller, M, Gehring, EM, Strutz-Seebohm, N, Ureche, ON, Ivanova, S, Semke, A, Lang, F, Seebohm, G & Lang, UE 2009, 'PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3', Psychopharmacology, vol. 206, no. 3, pp. 429-435. https://doi.org/10.1007/s00213-009-1621-5
Fedorenko O, Tang C, Sopjani M, Föller M, Gehring EM, Strutz-Seebohm N et al. PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. Psychopharmacology. 2009 Jul 31;206(3):429-435. https://doi.org/10.1007/s00213-009-1621-5
Fedorenko, Olga ; Tang, Cai ; Sopjani, Mentor ; Föller, Michael ; Gehring, Eva Maria ; Strutz-Seebohm, Nathalie ; Ureche, Oana N. ; Ivanova, Svetlana ; Semke, Arkadij ; Lang, Florian ; Seebohm, Guiscard ; Lang, Undine E. / PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. In: Psychopharmacology. 2009 ; Vol. 206, No. 3. pp. 429-435.
@article{ae76e65fcbe24455a01bd2921e910595,
title = "PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3",
abstract = "Introduction: According to previous observations, the gene encoding the phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) is associated with schizophrenia. Specifically, the mutation N251SPIP5K2A has been discovered in schizophrenic patients but not in healthy individuals. A defect of the excitatory amino acid transporter EAAT3 has similarly been implicated in the development of schizophrenia. The present study thus explored whether PIP5K2A is involved in the regulation of EAAT3 activity. Materials and methods: EAAT3 was expressed in Xenopus oocytes either without or with PIP5K2A, and EAAT3 transporter activity was estimated from the glutamate (2-mM)-induced current (Iglu) in dual electrode voltage clamp experiments. EAAT3 protein abundance in the cell membrane was estimated by Western blotting and confocal microscopy. Results: In EAAT3-expressing oocytes, Iglu was enhanced by coexpression of wild type PIP5K2A. Coexpression of the schizophrenia- associated mutant N251SPIP5K2A significantly decreased I glu in oocytes expressing EAAT3 with or without additional expression of wild type PIP5K2A. Thus, N251SPIP5K2A exerts a dominant inhibitory effect. Discussion: Membrane abundance of EAAT3 was increased by wild type PIP5K2A and decreased by N251SPIP5K2A in both EAAT3-expressing oocytes and human embryonic kidney cells. The present observations disclose a novel mechanism of EAAT3 regulation, which may contribute to the deranged regulation of excitability in schizophrenic patients.",
keywords = "Glutamate, Mutation, Neuroexcitability, PIP, Schizophrenia",
author = "Olga Fedorenko and Cai Tang and Mentor Sopjani and Michael F{\"o}ller and Gehring, {Eva Maria} and Nathalie Strutz-Seebohm and Ureche, {Oana N.} and Svetlana Ivanova and Arkadij Semke and Florian Lang and Guiscard Seebohm and Lang, {Undine E.}",
year = "2009",
month = "7",
day = "31",
doi = "10.1007/s00213-009-1621-5",
language = "English",
volume = "206",
pages = "429--435",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3

AU - Fedorenko, Olga

AU - Tang, Cai

AU - Sopjani, Mentor

AU - Föller, Michael

AU - Gehring, Eva Maria

AU - Strutz-Seebohm, Nathalie

AU - Ureche, Oana N.

AU - Ivanova, Svetlana

AU - Semke, Arkadij

AU - Lang, Florian

AU - Seebohm, Guiscard

AU - Lang, Undine E.

PY - 2009/7/31

Y1 - 2009/7/31

N2 - Introduction: According to previous observations, the gene encoding the phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) is associated with schizophrenia. Specifically, the mutation N251SPIP5K2A has been discovered in schizophrenic patients but not in healthy individuals. A defect of the excitatory amino acid transporter EAAT3 has similarly been implicated in the development of schizophrenia. The present study thus explored whether PIP5K2A is involved in the regulation of EAAT3 activity. Materials and methods: EAAT3 was expressed in Xenopus oocytes either without or with PIP5K2A, and EAAT3 transporter activity was estimated from the glutamate (2-mM)-induced current (Iglu) in dual electrode voltage clamp experiments. EAAT3 protein abundance in the cell membrane was estimated by Western blotting and confocal microscopy. Results: In EAAT3-expressing oocytes, Iglu was enhanced by coexpression of wild type PIP5K2A. Coexpression of the schizophrenia- associated mutant N251SPIP5K2A significantly decreased I glu in oocytes expressing EAAT3 with or without additional expression of wild type PIP5K2A. Thus, N251SPIP5K2A exerts a dominant inhibitory effect. Discussion: Membrane abundance of EAAT3 was increased by wild type PIP5K2A and decreased by N251SPIP5K2A in both EAAT3-expressing oocytes and human embryonic kidney cells. The present observations disclose a novel mechanism of EAAT3 regulation, which may contribute to the deranged regulation of excitability in schizophrenic patients.

AB - Introduction: According to previous observations, the gene encoding the phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) is associated with schizophrenia. Specifically, the mutation N251SPIP5K2A has been discovered in schizophrenic patients but not in healthy individuals. A defect of the excitatory amino acid transporter EAAT3 has similarly been implicated in the development of schizophrenia. The present study thus explored whether PIP5K2A is involved in the regulation of EAAT3 activity. Materials and methods: EAAT3 was expressed in Xenopus oocytes either without or with PIP5K2A, and EAAT3 transporter activity was estimated from the glutamate (2-mM)-induced current (Iglu) in dual electrode voltage clamp experiments. EAAT3 protein abundance in the cell membrane was estimated by Western blotting and confocal microscopy. Results: In EAAT3-expressing oocytes, Iglu was enhanced by coexpression of wild type PIP5K2A. Coexpression of the schizophrenia- associated mutant N251SPIP5K2A significantly decreased I glu in oocytes expressing EAAT3 with or without additional expression of wild type PIP5K2A. Thus, N251SPIP5K2A exerts a dominant inhibitory effect. Discussion: Membrane abundance of EAAT3 was increased by wild type PIP5K2A and decreased by N251SPIP5K2A in both EAAT3-expressing oocytes and human embryonic kidney cells. The present observations disclose a novel mechanism of EAAT3 regulation, which may contribute to the deranged regulation of excitability in schizophrenic patients.

KW - Glutamate

KW - Mutation

KW - Neuroexcitability

KW - PIP

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=70349562479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349562479&partnerID=8YFLogxK

U2 - 10.1007/s00213-009-1621-5

DO - 10.1007/s00213-009-1621-5

M3 - Article

C2 - 19644675

AN - SCOPUS:70349562479

VL - 206

SP - 429

EP - 435

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 3

ER -