MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates G protein‐mediated constitutive inhibition of calcium channels
F Bertaso, Y Lill, JM Airas, J Espeut… - Journal of …, 2006 - Wiley Online Library
F Bertaso, Y Lill, JM Airas, J Espeut, J Blahos, J Bockaert, L Fagni, H Betz, O El Far
Journal of neurochemistry, 2006•Wiley Online LibraryWe have previously shown that the interaction of Ca2+/calmodulin with the metabotropic
glutamate receptor type 7 (mGluR7) promotes the G‐protein‐mediated inhibition of voltage‐
sensitive Ca2+ channels (VSCCs) seen upon agonist activation. Here, we performed a yeast
two‐hybrid screen of a new‐born rat brain cDNA library using the cytoplasmic C‐terminal tail
of mGluR7 as bait and identified macrophage myristoylated alanine‐rich c‐kinase substrate
(MacMARCKS) as a binding protein. The interaction was confirmed in vitro and in vivo by …
glutamate receptor type 7 (mGluR7) promotes the G‐protein‐mediated inhibition of voltage‐
sensitive Ca2+ channels (VSCCs) seen upon agonist activation. Here, we performed a yeast
two‐hybrid screen of a new‐born rat brain cDNA library using the cytoplasmic C‐terminal tail
of mGluR7 as bait and identified macrophage myristoylated alanine‐rich c‐kinase substrate
(MacMARCKS) as a binding protein. The interaction was confirmed in vitro and in vivo by …
Abstract
We have previously shown that the interaction of Ca2+/calmodulin with the metabotropic glutamate receptor type 7 (mGluR7) promotes the G‐protein‐mediated inhibition of voltage‐sensitive Ca2+ channels (VSCCs) seen upon agonist activation. Here, we performed a yeast two‐hybrid screen of a new‐born rat brain cDNA library using the cytoplasmic C‐terminal tail of mGluR7 as bait and identified macrophage myristoylated alanine‐rich c‐kinase substrate (MacMARCKS) as a binding protein. The interaction was confirmed in vitro and in vivo by pull‐down assays, immunoprecipitation, and colocalization of mGluR7 and MacMARCKS in transfected HEK293 cells and cultured cerebellar granule cells. Binding of MacMARCKS to mGluR7 was antagonized by Ca2+/calmodulin. In neurons, cotransfection of MacMARCKS with mGluR7, but not mGluR7 mutants unable to bind MacMARCKS, reduced the G‐protein‐mediated tonic inhibition of VSCCs in the absence of mGluR7 agonist. These results suggest that competitive interactions of Ca2+/calmodulin and MacMARCKS with mGluR7 control the tonic inhibition of VSCCs by G‐proteins.
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