EC:2.7.11.17 - FACTA Search

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

It has been shown in vivo that Wnt5a gradients surround the corpus callosum and guide callosal axons after the midline (postcrossing) by Wnt5a-induced repulsion via Ryk receptors. In dissociated cortical cultures we showed that Wnt5a simultaneously promotes axon outgrowth and repulsion by calcium signaling. Here to test the role of Wnt5a/calcium signaling in a complex in vivo environment we used sensorimotor cortical slices containing the developing corpus callosum. Plasmids encoding the cytoplasmic marker DsRed and the genetically encoded calcium indicator GCaMP2 were electroporated into one cortical hemisphere. Postcrossing callosal axons grew 50% faster than pre-crossing axons and higher frequencies of calcium transients in axons and growth cones correlated well with outgrowth. Application of pharmacological inhibitors to the slices showed that signaling pathways involving calcium release through IP3 receptors and calcium entry through TRP channels regulate post-crossing axon outgrowth and guidance. Co-electroporation of Ryk siRNA and DsRed revealed that knock down of the Ryk receptor reduced outgrowth rates of postcrossing but not precrossing axons by 50% and caused axon misrouting. Guidance errors in axons with Ryk knockdown resulted from reduced calcium activity. In the corpus callosum CaMKII inhibition reduced the outgrowth rate of postcrossing (but not precrossing) axons and caused severe guidance errors which resulted from reduced CaMKII-dependent repulsion downstream of Wnt/calcium. We show for the first time that Wnt/Ryk calcium signaling mechanisms regulating axon outgrowth and repulsion in cortical cultures are also essential for the proper growth and guidance of postcrossing callosal axons which involve axon repulsion through CaMKII.
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PMID:Wnt/calcium signaling mediates axon growth and guidance in the developing corpus callosum. 2093 61

(1) BACKGROUND: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca(2+)-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) METHODS: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca(2+)]i). Flow cytometry was used to analyze cell cycle; (3) RESULTS: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca(2+)]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) CONCLUSIONS: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.
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PMID:Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer. 2702 18

Unregulated Ca²⁺ influx affects intracellular Ca²⁺ homoeostasis, which may lead to neuronal death. In Drosophila, following the activation of rhodopsin the TRP Ca²⁺ channel is open to mediate the light-dependent depolarization. A constitutively active TRP channel triggers the degeneration of Trp^P365 /+ photoreceptors. To explore retinal degeneration, we employed a multidisciplinary approach including live imaging using GFP tagged actin and arrestin 2. Importantly, we demonstrate that the major rhodopsin (Rh1) was greatly reduced before the onset of rhabdomere degeneration; a great reduction of Rh1 affects the maintenance of rhabdomere leading to degeneration of photoreceptors. Trp^P365 /+ also led to the up-regulation of CaMKII, which is beneficial as suppression of CaMKII accelerated retinal degeneration. We explored the regulation of TRP by investigating the genetic interaction between Trp^P365 /+ and mutants affecting the turnover of diacylglycerol (DAG). We show a loss of phospholipase C in norpA^P24 exhibited a great reduction of the DAG content delayed degeneration of Trp^P365 /+ photoreceptors. In contrast, knockdown or mutations in DAG lipase (InaE) that is accompanied by slightly reduced levels of most DAG but an increased level of DAG 34:1, exacerbated retinal degeneration of Trp^P365 /+. Together, our findings support the notion that DAG plays a role in regulating TRP. Interestingly, DAG lipase is likely required during photoreceptor development as Trp^P365 /+; inaE^N125 double mutants contained severely degenerated rhabdomeres.
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PMID:Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca²⁺ Channel in Drosophila. 3320 Jun 58