KRIP6: A novel BTB/kelch protein regulating function of kainate receptors

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

doi:10.1016/j.mcn.2006.12.003

Cited by 42 publications

(42 citation statements)

References 55 publications

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“…1). At least six genes may be involved in brain development and function, particularly: DCUN1D1, for which the mouse ortholog is expressed in proliferating neuroblasts [4]; DVL3, a regulator of cell proliferation and neuroblast specification [5]; several genes belonging to the serotonin receptor family (HTR3C, HTR3D, HTR3E); KLHL24, involved in functional regulation of glutamate receptors [6]; MAP6D1, a neuronal protein that binds microtubules and plays a role in synaptic function in neuritis [7].…”

Section: Discussionmentioning

confidence: 99%

3q26.33–3q27.2 microdeletion: A new microdeletion syndrome?

Mandrile

Dubois

Hoffman

et al. 2013

European Journal of Medical Genetics

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Section: Discussionmentioning

confidence: 99%

3q26.33–3q27.2 microdeletion: A new microdeletion syndrome?

Mandrile

Dubois

Hoffman

et al. 2013

European Journal of Medical Genetics

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“…It has also been proposed that the specific behavior of synaptic KARs could be determined by the binding of modulatory proteins to the receptors' cytoplasmic domains. However, the alterations of KAR gating properties induced by interacting proteins reported so far are unlikely to be the main determinant for the differences between KAR-EPSCs and recombinant KAR-mediated currents (Garcia et al, 1998;Bowie et al, 2003;Laezza et al, 2007).…”

Section: Introductionmentioning

confidence: 91%

GluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents

Barberis

Sachidhanandam²,

Mulle³

2008

Journal of Neuroscience

126

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Kainate receptors (KARs) are ionotropic glutamate receptors contributing to EPSCs with a slow-decaying component that is likely essential for synaptic integration. The slow kinetics of KAR-EPSCs markedly contrasts with the fast kinetics reported for recombinant KARs expressed in heterologous systems, for reasons that remain unexplained. Here we have studied the properties of recombinant heteromeric GluR6/KA2 receptors, which compose synaptic KARs. We report that, in response to brief glutamate applications, currents mediated by recombinant GluR6/KA2 receptors, but not GluR6 receptors, decay with a time course similar to KAR-EPSCs. Model simulations suggest that, after brief agonist exposures, GluR6/KA2 currents undergo slow deactivation caused by the stabilization of partially bound open states. We propose, therefore, that the GluR6/KA2 gating features could contribute to the slow KAR-EPSC decay kinetics.

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“…Conversely, Y2H screens have provided evidence for a direct interaction between GluK2a and PDZ domaincontaining proteins (PSD-95, syntenin, GRIP, and PICK1) (21,22), through the last four amino acids of GluK2a. In addition, two proteins of the BTB-Kelch family, actinfilin and KRIP6, bind to the C-terminal domain of GluK2a (10,23), although the exact sequence of interaction has not been identified. Finally, a recent study has indicated that Neto2, identified by a Y2H screen acts as an auxilliary protein for KARs (24).…”

Section: Discussionmentioning

confidence: 99%

Profilin II Regulates the Exocytosis of Kainate Glutamate Receptors

Mondin

Carta

Normand

et al. 2010

Journal of Biological Chemistry

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The trafficking of ionotropic glutamate receptors to and from synaptic sites is regulated by proteins that interact with their cytoplasmic C-terminal domain. Profilin IIa (PfnIIa), an actin-binding protein expressed in the brain and recruited to synapses in an activity-dependent manner, was shown previously to interact with the C-terminal domain of the GluK2b subunit splice variant of kainate receptors (KARs). Here, we characterize this interaction and examine the role of PfnIIa in the regulation of KAR trafficking. PfnIIa directly and specifically binds to the C-terminal domain of GluK2b through a diproline motif. Expression of PfnIIa in transfected COS-7 cells and in cultured hippocampal neurons from PfnII-deficient mice decreases the level of extracellular of homomeric GluK2b as well as heteromeric GluK2a/GluK2b KARs. Our data suggest a novel mechanism by which PfnIIa exerts a dual role on the trafficking of KARs, by a generic inhibition of clathrin-mediated endocytosis through its interaction with dynamin-1, and by controlling KARs exocytosis through a direct and specific interaction with GluK2b. Kainate receptors (KARs)2 compose a family of ionotropic glutamate receptors, which play an important role in the regulation of synaptic transmission and neuronal excitability (1, 2). At variance with the closely related family of AMPA receptors, the main postsynaptic receptors involved in fast synaptic transmission, KARs exert their function by acting at either pre-or postsynaptic sites. Because their physiological functions critically depend on their specific localization as well as their density in these different neuronal compartments, it is important to better understand the mechanisms by which their trafficking is regulated in neurons. KARs are heterotetrameric receptor channels composed of various combinations of five subunits GluK1, GluK2, GluK3, GluK4, and GluK5 (formerly referred as GluR5, GluR6, GluR7, KA1, and KA2, respectively). The diversity of KARs is increased by the existence of splice variants for GluK1, GluK2, and GluK3 subunits. KAR subunits isoforms display different levels of expression at the plasma membrane depending on the alternative splicing of their C terminus (3-5). When expressed as homomers in heterologous cells or in cultured neurons, GluK2a is highly addressed to the plasma membrane, whereas GluK2b is present at low levels (3, 4, 6). The low level of expression of homomeric GluR6b can be explained by restricted export of the subunit from the endoplasmic reticulum (3). Native KARs likely exist as heteromers of different GluK subunits, as well as of different splice variants of the same GluK subunit, as for instance, in the case of GluK2a/GluK2b heteromers, which form native KARs (7). Oligomerization of KAR subunits plays a major role in their surface expression (4, 8). The regulation of ionotropic glutamate receptors trafficking to the cell surface is probably controlled by a combination of endoplasmic reticulum retention and export signals, as well as by domain-specific protein inter...

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KRIP6: A novel BTB/kelch protein regulating function of kainate receptors

Cited by 42 publications

References 55 publications

3q26.33–3q27.2 microdeletion: A new microdeletion syndrome?

3q26.33–3q27.2 microdeletion: A new microdeletion syndrome?

GluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents

Profilin II Regulates the Exocytosis of Kainate Glutamate Receptors

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