checkpoint kinase

Wednesday, July 18, 2012

SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity.

SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity.

Nat Neurosci. 2012 Apr 22;

Authors: Chamberlain SE, Gonz�lez-Gonz�lez IM, Wilkinson KA, Konopacki FA, Kantamneni S, Henley JM, Mellor JR

Abstract
Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses. Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

PMID: 22522402 [PubMed - as supplied by publisher]

ATPase ampa receptor potassium channel genes

Calcium-permeable AMPA receptors in the VTA and nucleus accumbens after cocaine exposure: when, how, and why?

Calcium-permeable AMPA receptors in the VTA and nucleus accumbens after cocaine exposure: when, how, and why?

Front Mol Neurosci. 2012;5:72

Authors: Wolf ME, Tseng KY

Abstract
In animal models of drug addiction, cocaine exposure has been shown to increase levels of calcium-permeable AMPA receptors (CP-AMPARs) in two brain regions that are critical for motivation and reward-the ventral tegmental area (VTA) and the nucleus accumbens (NAc). This review compares CP-AMPAR plasticity in the two brain regions and addresses its functional significance. In VTA dopamine neurons, cocaine exposure results in synaptic insertion of high conductance CP-AMPARs in exchange for lower conductance calcium-impermeable AMPARs (CI-AMPARs). This plasticity is rapid in onset (hours), GluA2-dependent, and can be observed with a single cocaine injection. Whereas it is short-lived after experimenter-administered cocaine, it persists for months after cocaine self-administration. In addition to strengthening synapses and altering Ca(2+) signaling, CP-AMPAR insertion alters subsequent induction of plasticity at VTA synapses. However, CP-AMPAR insertion is unlikely to mediate the increased DA cell activity that occurs during early withdrawal from cocaine exposure. Metabotropic glutamate receptor 1 (mGluR1) exerts a negative influence on CP-AMPAR accumulation in the VTA. Acutely, mGluR1 stimulation elicits a form of LTD resulting from CP-AMPAR removal and CI-AMPAR insertion. In medium spiny neurons (MSNs) of the NAc, extended access cocaine self-administration is required to increase CP-AMPAR levels. This is first detected after approximately a month of withdrawal and then persists. Once present in NAc synapses, CP-AMPARs mediate the expression of incubation of cue-induced cocaine craving. The mechanism of their accumulation may be GluA1-dependent, which differs from that observed in the VTA. However, similar to VTA, mGluR1 stimulation removes CP-AMPARs from MSN synapses. Loss of mGluR1 tone during cocaine withdrawal may contribute to CP-AMPAR accumulation in the NAc. Thus, results in both brain regions point to the possibility of using positive modulators of mGluR1 as treatments for cocaine addiction.

PMID: 22754497 [PubMed - as supplied by publisher]

Catalog Peptide Peptide products ion channel definition

Pharmacological and structural characterization of conformationally restricted (S)-glutamate analogues at ionotropic glutamate receptors.

Pharmacological and structural characterization of conformationally restricted (S)-glutamate analogues at ionotropic glutamate receptors.
J Struct Biol. 2012 Jul 9;
Authors: Juknait? L, Venskutonyt? R, Assaf Z, Faure S, Gefflaut T, Aitken DJ, Nielsen B, Gajhede M, Kastrup JS, Bunch L, Frydenvang K, Pickering DS
Abstract
Conformationally restricted glutamate analogues have been pharmacologically characterized at AMPA and kainate receptors and the crystal structures have been solved of the ligand (2S,1'R,2'S)-2-(2'-carboxycyclobutyl)glycine (CBG-IV) in complex with the ligand binding domains of the AMPA receptor GluA2 and the kainate receptor GluK3. These structures show that CBG-IV interacts with the binding pocket in the same way as (S)-glutamate. The binding affinities reveal that CBG-IV has high affinity at the AMPA and kainate receptor subtypes. Appreciable binding affinity of CBG-IV was not observed at NMDA receptors, where the introduction of the carbocyclic ring is expected to lead to a steric clash with binding site residues. CBG-IV was demonstrated to be an agonist at both GluA2 and the kainate receptor GluK1. CBG-IV showed high affinity binding to GluK1 compared to GluA2, GluK2 and GluK3, which exhibited lower affinity for CBG-IV. The structure of GluA2 LBD and GluK3 LBD in complex with CBG-IV revealed similar binding site interactions to those of (S)-glutamate. No major conformational rearrangements compared to the (S)-glutamate bound conformation were found in GluK3 in order to accommodate CBG-IV, in contrast with GluA2 where a shift in lobe D2 binding site residues occurs, leading to an increased binding cavity volume compared to the (S)-glutamate bound structure.

PMID: 22789682 [PubMed - as supplied by publisher]
ampa receptor potassium channel genes Kainate Receptor

Neuronal Signaling and MEK Signaling Pathway rosuvastatin in myocardial infarction

As reported elsewhere, after a median comply with up of 1.9 many years, MEK Signaling Pathway rosuvastatin use was related with a 54% reduction in myocardial infarction, a 48% reduction in stroke, a 46% reduction in revascularization, a 43% reduction in venous thromboembolism, and a 20% reduction in complete mortality.

Maraviroc GPCR Signaling being involved amongst other isozymes in fertilization processes

Even although GPCR Signaling is secreted in saliva and milk, its precise role is not acknowledged. 8 hCA XIII is predominantly identified in the genito urinary tract, being involved amongst other isozymes in fertilization processes.

Dietary calcium induced cytological and biochemical changes in thyroid.

Dietary calcium induced cytological and biochemical changes in thyroid.

Environ Toxicol Pharmacol. 2012 Jun 26;34(2):454-465

Authors: Chandra AK, Goswami H, Sengupta P

Abstract
Certain epidemiological studies revealed correlation between hard water consumption (with high calcium) and thyroid size of the population, though the possible alterations in thyroid physiology upon calcium exposure are still inconclusive. Adult male Wistar strain rats were subjected to calcium treatment at the doses of 0.5g%, 1.0g% and 1.5g% calcium chloride (CaCl(2)) for 60 days. The parameters studied were - thyroid gland weight, histopathology, histomorphometry; thyroid peroxidase (TPO), 5'-deiodinase I (DI), sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase) activities; serum total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), thyroid stimulating hormone (TSH) levels. Enlargement of thyroid with hypertrophic and hyperplastic changes, retarded TPO and 5'-DI but enhanced Na(+)-K(+)-ATPase activities, augmented serum total and free T4 and TSH but decreased total and free T3 levels and low T3/T4 ratio (T3:T4) were observed in the treated groups. All these findings indicate development of goitrogenesis upon exposure to excessive dietary calcium.

PMID: 22789468 [PubMed - as supplied by publisher]

ATPase ampa receptor potassium channel genes

Involvement of nicotinic acetylcholine receptor in the proliferation of mouse induced pluripotent stem cells.

Involvement of nicotinic acetylcholine receptor in the proliferation of mouse induced pluripotent stem cells.

Life Sci. 2012 May 15;90(17-18):637-48

Authors: Ishizuka T, Ozawa A, Goshima H, Watanabe Y

Abstract
AIMS: As the clinical use of induced pluripotent stem (iPS) cells may have the potential to overcome current obstacles in stem cell-based therapy, the molecular mechanisms that regulate the proliferation of iPS cells are of great interest. However, to our knowledge, no previous studies have examined whether stimulation with nicotinic acetylcholine receptor (nAchR) enhances the growth of iPS cells. In the present study, we examined the involvement of nAchR in the proliferation of mouse iPS cells.
MAIN METHODS: We performed immunofluorescence staining to determine whether mouse iPS cells could express nAchRs. Mouse iPS cells were treated with nicotine for 24h under feeder-free conditions in the presence of leukemia inhibitory factor (LIF). The DNA synthesis was examined by the BrdU incorporation assay. Intracellular calcium levels were measured using Fluo-4-acetoxymethyl (a cell-permeable calcium indicator). In addition, we examined the involvement of the CaMK? pathway in nicotine-enhanced proliferation of mouse iPS cells.
KEY FINDINGS: The fluorescence images revealed that ?(4)-nAchR and ?(7)-nAchR are expressed on mouse iPS cells. Treatment of the cells with 300nM nicotine significantly increases DNA synthesis. This is significantly inhibited by pretreatment with antagonists of ?(4)-nAchR and ?(7)-nAchR or a CaMK? inhibitor. In addition, treatment with nicotine increases the intracellular Ca(2+) level dose-dependently in mouse iPS cells. Treatment with nicotine significantly enhances CaMK? phosphorylation.
SIGNIFICANCE: The present study indicates that stimulation of ?(4)-nAchR and ?(7)-nAchR may lead to a significant increase in the rate of mouse iPS cell proliferation through enhancement of the CaMK? signaling pathway.

PMID: 22483693 [PubMed - indexed for MEDLINE]

Potassium Channel AMPA Receptor ATPase