KRIP6

A novel BTB/kelch protein regulating function of kainate receptors

Fernanda Laezza, Timothy J. Wilding, Sunitha Sequeira, Françoise Coussen, Xue Zhao Zhang, Rona Hill-Robinson, Christophe Mulle, James E. Huettner, Ann Marie Craig

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.

Original languageEnglish (US)
Pages (from-to)539-550
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume34
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

Fingerprint

Kainic Acid Receptors
Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Proteins
N-Methyl-D-Aspartate Receptors
Yeasts
Neurons
Brain

Keywords

  • BTB/kelch proteins
  • Desensitization
  • GluR6
  • Hippocampus
  • Kainate receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Laezza, F., Wilding, T. J., Sequeira, S., Coussen, F., Zhang, X. Z., Hill-Robinson, R., ... Craig, A. M. (2007). KRIP6: A novel BTB/kelch protein regulating function of kainate receptors. Molecular and Cellular Neuroscience, 34(4), 539-550. https://doi.org/10.1016/j.mcn.2006.12.003

KRIP6 : A novel BTB/kelch protein regulating function of kainate receptors. / Laezza, Fernanda; Wilding, Timothy J.; Sequeira, Sunitha; Coussen, Françoise; Zhang, Xue Zhao; Hill-Robinson, Rona; Mulle, Christophe; Huettner, James E.; Craig, Ann Marie.

In: Molecular and Cellular Neuroscience, Vol. 34, No. 4, 04.2007, p. 539-550.

Research output: Contribution to journalArticle

Laezza, F, Wilding, TJ, Sequeira, S, Coussen, F, Zhang, XZ, Hill-Robinson, R, Mulle, C, Huettner, JE & Craig, AM 2007, 'KRIP6: A novel BTB/kelch protein regulating function of kainate receptors', Molecular and Cellular Neuroscience, vol. 34, no. 4, pp. 539-550. https://doi.org/10.1016/j.mcn.2006.12.003
Laezza, Fernanda ; Wilding, Timothy J. ; Sequeira, Sunitha ; Coussen, Françoise ; Zhang, Xue Zhao ; Hill-Robinson, Rona ; Mulle, Christophe ; Huettner, James E. ; Craig, Ann Marie. / KRIP6 : A novel BTB/kelch protein regulating function of kainate receptors. In: Molecular and Cellular Neuroscience. 2007 ; Vol. 34, No. 4. pp. 539-550.
@article{ba1681b66c14493489be69c91c15c4fa,
title = "KRIP6: A novel BTB/kelch protein regulating function of kainate receptors",
abstract = "Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.",
keywords = "BTB/kelch proteins, Desensitization, GluR6, Hippocampus, Kainate receptors",
author = "Fernanda Laezza and Wilding, {Timothy J.} and Sunitha Sequeira and Fran{\cc}oise Coussen and Zhang, {Xue Zhao} and Rona Hill-Robinson and Christophe Mulle and Huettner, {James E.} and Craig, {Ann Marie}",
year = "2007",
month = "4",
doi = "10.1016/j.mcn.2006.12.003",
language = "English (US)",
volume = "34",
pages = "539--550",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - KRIP6

T2 - A novel BTB/kelch protein regulating function of kainate receptors

AU - Laezza, Fernanda

AU - Wilding, Timothy J.

AU - Sequeira, Sunitha

AU - Coussen, Françoise

AU - Zhang, Xue Zhao

AU - Hill-Robinson, Rona

AU - Mulle, Christophe

AU - Huettner, James E.

AU - Craig, Ann Marie

PY - 2007/4

Y1 - 2007/4

N2 - Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.

AB - Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.

KW - BTB/kelch proteins

KW - Desensitization

KW - GluR6

KW - Hippocampus

KW - Kainate receptors

UR - http://www.scopus.com/inward/record.url?scp=33947606924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947606924&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2006.12.003

DO - 10.1016/j.mcn.2006.12.003

M3 - Article

VL - 34

SP - 539

EP - 550

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

IS - 4

ER -