Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization histochemistry and immunocytochemistry were used to examine lamina- and cell-specific expression of glutamate receptor (GluR) mRNAs and polypeptide subunits in motor and somatosensory cortex of macaque monkeys. Radioactive complementary RNA (cRNA) probes were prepared from cDNAs specific for alpha-amino-3-hydroxy-5-methylisoxozolepropionate (AMPA)/kainate (GluR1-GluR4), kainate (GluR5-GluR7), and N-methyl-D-aspartate (NMDA; NR1, NR2A-NR2D) receptor subunits. AMPA/kainate and NR1, NR2A, and NR2B receptor transcripts show higher expression than other transcripts. All transcripts show lamina-specific patterns of distribution. GluR2 and GluR4 mRNAs show higher expression than do GluR1 and GluR3 mRNAs. GluR6 transcript expression is higher than that of GluR5 and GluR7. NR1 mRNA expression is much higher than that of NR2 mRNAs. NR2C subunit expression is very low except for a very distinct band of high expression in layer IV of area 3b. Immunocytochemistry, using subunit-specific antisera and double labeling for calbindin, parvalbumin, or alpha type II Ca2+/calmodulin-dependent protein kinase (CaMKII-alpha), allowed identification of cell types expressing different subunit genes. GluR1 and GluR5/6/7 immunoreactivity is found in both pyramidal cells and gamma-amino butyric acid (GABA) cells; GluR2/3 immunoreactivity is preferentially found in pyramidal cells, whereas GluR4 immunoreactivity is largely restricted to GABA cells; NMDA receptor subunit immunoreactivity is far greater in excitatory cells than in GABA cells. The density of expression of AMPA/kainate, kainate, and NMDA receptor subunit mRNAs differed within and across the architectonic fields of sensory-motor cortex. This finding and the lamina- and cell-specific patterns of expression suggest assembly of functional receptors from different arrangements of available subunits in specific neuronal populations.
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PMID:Laminar and cellular distribution of AMPA, kainate, and NMDA receptor subunits in monkey sensory-motor cortex. 1023 40

In the developing cerebellum, switching of subunit composition of NMDA receptors occurs in granule cells from NR2B subunit-containing receptors to NR2C subunit-containing receptors. This switching of subunit composition plays an important role in the establishment of functional mossy fiber-granule cell synaptic transmission in the mature cerebellar network. The mechanism underlying NR2C upregulation in developing granule cells, however, has to date remained to be determined. In granule cells cultured in low (5 mm) KCl, brain-derived neurotrophic factor (BDNF) upregulated NR2C mRNA via the TrkB-extracellular signal-regulated kinase (ERK) 1/2 cascade and promoted the formation of an NR2C-containing NMDA receptor complex. In granule cells cultured in high (25 mm) KCl, depolarization stimulated voltage-sensitive Ca2+ channels. The resultant increase in intracellular Ca2+ activated Ca2+/calmodulin-dependent calcineurin phosphatase and blocked NR2C mRNA upregulation. Interestingly, the depolarization-induced Ca2+ increase simultaneously upregulated BDNF mRNA via Ca2+/calmodulin-dependent protein kinase (CaMK). Consequently, when calcineurin was inhibited by its inhibitor FK506 under the depolarizing condition, the CaMK-mediated increase in BDNF became a stimulatory signal, and the endogenous BDNF autocrine system was capable of upregulating NR2C mRNA via the common TrkB-ERK cascade. The importance of the BDNF-TrkB pathway was further supported by a significant reduction in NR2C in normally migrated granule cells of TrkB(-/-) knock-out mice in vivo. The convergent mechanism of the BDNF and Ca2+ signaling cascades thus plays an important regulatory role in NR2C induction in granule cells during cerebellar development.
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PMID:Neuronal depolarization controls brain-derived neurotrophic factor-induced upregulation of NR2C NMDA receptor via calcineurin signaling. 1622 64