SAP90 Binds and Clusters Kainate Receptors Causing Incomplete Desensitization

Garcia, Elizabeth; Mehta, Sunil; Blair, Leslie A.C.; Wells, David G.; Shang, Junlong; Fukushima, Toshikazu; Fallon, Justin R.; Garner, Craig C.; Marshall, John

doi:10.1016/s0896-6273(00)80590-5

Cited by 246 publications

(244 citation statements)

References 67 publications

(15 reference statements)

Supporting

Mentioning

219

Contrasting

Unclassified

Order By: Relevance

“…This result agrees with an earlier study (Bowie et al 2003) of channel regulation that used high speed agonist applications to outside-out macropatches. Bowie and colleagues (2003) found no change in the time constant of desensitization following modulation of homomeric GluR6 channels by extracellular treatment with Con A (Huettner, 1990), or by co-expression of the cytoplasmic PDZ domain protein PSD-95 (Garcia et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, we find that KRIP6 acts to reduce kainate receptor-mediated peak currents in hippocampal neurons. The PDZ domain proteins PSD-95 and syntenin also bind GluR5 and GluR6 and may modulate receptor function (Bowie et al, 2003;Garcia et al, 1998;Hirbec et al, 2003). KRIP6 differs from these other kainate receptor interacting proteins in that it binds the C-terminal domain of GluR6 but not other kainate, AMPA, or NMDA receptor subunits tested, and thus may function more specifically to regulate only GluR6-containing kainate receptors.…”

Section: Discussionmentioning

confidence: 99%

“…1C, D). Whereas the extreme C-terminal residues of GluR6a ending in -ETMA interact with the PDZ domains of PSD-95, PICK1, and GRIP (Garcia et al, 1998;Hirbec et al, 2003), the last 10 aa were not required for interacting with KRIP6. When co-transformed with , the first 58 aa of the GluR6a C-terminus mediated equal β-galactosidase marker activity compared with the full 68 aa (respectively 94 ± 15 and 109 ± 15, arbitrary units, p=0.5, t-test).…”

Section: Krip6 Is a Btb/kelch Protein Interacting With Glur6mentioning

confidence: 93%

“…We obtained two positive clones, one coding for the protein PSD-95, and the other consisting of a 540 bp cDNA fragment of unknown function. Since the interaction of GluR6 and PSD-95 was described previously (Garcia et al, 1998), we focused our studies on the novel clone. This cDNA is homologous to a clone isolated from mouse testis (accession # AK015239) and to a more recently deposited clone isolated from rat uterus (accession # NM_181473), both of unknown function.…”

Section: Krip6 Is a Btb/kelch Protein Interacting With Glur6mentioning

confidence: 99%

“…The majority of proteins so far identified to directly bind and regulate kainate receptors are known members of the PDZdomain family first studied as regulators of AMPA and/or NMDA receptors. PSD-95 binds to the C-termini of GluR6 and KA2 kainate receptor subunits (Garcia et al, 1998), and GRIP and PICK1 to the C-termini of GluR6 and GluR5 (Hirbec et al, 2003), an interaction required to maintain kainate receptor synaptic function at mossy fiber to CA3 inputs (Hirbec et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Laezza

Wilding

Sequeira

et al. 2007

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Krip6 Is a Btb/kelch Protein Interacting With Glur6mentioning

confidence: 93%

Section: Krip6 Is a Btb/kelch Protein Interacting With Glur6mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Laezza

Wilding

Sequeira

et al. 2007

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

show abstract

Drosophila larval neuromuscular junction: Molecular components and mechanisms underlying synaptic plasticity

Koh

Gramates

Budnik

2000

Microsc. Res. Tech.

View full text Add to dashboard Cite

Understanding the mechanisms that mediate synaptic plasticity is a primary goal of molecular neuroscience. The Drosophila larval neuromuscular junction provides a particularly useful model for investigating the roles of synaptic components in both structural and functional plasticity. The powerful molecular genetics of this system makes it possible to uncover new synaptic components and signaling molecules, as well as their function in the intact organism. Together with the mouse hippocampus and Aplysia dissociated cell culture, the Drosophila larval neuromuscular junction has been among the most valuable model systems for examining the molecular and cellular basis of neuronal plasticity. Microsc. Res. Tech. 49:14–25, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Differential expression of the PSD-95 gene family in electrosensory neurons

2000

View full text Add to dashboard Cite

The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.

show abstract

SAP90 Binds and Clusters Kainate Receptors Causing Incomplete Desensitization

Cited by 246 publications

References 67 publications

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

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

Drosophila larval neuromuscular junction: Molecular components and mechanisms underlying synaptic plasticity

Differential expression of the PSD-95 gene family in electrosensory neurons

Contact Info

Product

Resources

About