Calmodulin activity regulates group I metabotropic glutamate receptor‐mediated signal transduction and synaptic depression |
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Authors: | Ferzin Sethna Ming Zhang Hanoch Kaphzan Eric Klann Dawn Autio Charles L Cox Hongbing Wang |
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Institution: | 1. Genetics Program, Michigan State University, East Lansing, Michigan;2. Department of Physiology, Michigan State University, East Lansing, Michigan;3. Neuroscience Program, Michigan State University, East Lansing, Michigan;4. Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China;5. Center for Neural Science, New York University, New York, New York;6. Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel |
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Abstract: | Group I metabotropic glutamate receptors (mGluR), including mGluR1 and mGluR 5 (mGluR1/5), are coupled to Gq and modulate activity‐dependent synaptic plasticity. Direct activation of mGluR1/5 causes protein translation‐dependent long‐term depression (LTD). Although it has been established that intracellular Ca2+ and the Gq‐regulated signaling molecules are required for mGluR1/5 LTD, whether and how Ca2+ regulates Gq signaling and upregulation of protein expression remain unknown. Through pharmacological inhibition, we tested the function of the Ca2+ sensor calmodulin (CaM) in intracellular signaling triggered by the activation of mGluR1/5. CaM inhibitor N‐4‐aminobutyl]‐5‐chloro‐2‐naphthalenesulfonamide hydrochloride (W13) suppressed the mGluR1/5‐stimulated activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and p70‐S6 kinase 1 (S6K1) in hippocampal neurons. W13 also blocked the mGluR1/5 agonist‐induced synaptic depression in hippocampal slices and in anesthetized mice. Consistent with the function of CaM, inhibiting the downstream targets Ca2+/CaM‐dependent protein kinases (CaMK) blocked ERK1/2 and S6K1 activation. Furthermore, disruption of the CaM–CaMK–ERK1/2 signaling cascade suppressed the mGluR1/5‐stimulated upregulation of Arc expression. Altogether, our data suggest CaM as a new Gq signaling component for coupling Ca2+ and protein upregulation and regulating mGluR1/5‐mediated synaptic modification. © 2016 Wiley Periodicals, Inc. |
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Keywords: | AB_331647 AB_823494 AB_2265913 AB_823592 AB_887694 Arc calmodulin mGluR1/5 synaptic depression ERK1/2 signal transduction |
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