Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons.

@article{citeulike:2425890, abstract = {As the Ca2+-sensor for Ca2+-dependent inactivation, calmodulin (CaM) has been proposed, but never definitively demonstrated, to be a constitutive Ca(V)1.2 Ca2+ channel subunit. Here we show that CaM is associated with the Ca(V)1.2 pore-forming alpha1C subunit in brain in a Ca2+-independent manner. Within its CaM binding pocket, alpha1C has been proposed to contain a membrane targeting domain. Because ion channel subunits assemble early during channel biosynthesis, we postulated that this association with CaM could afford the opportunity for Ca2+-dependent regulation of membrane targeting. We showed that the isolated domain functioned as a Ca2+/CaM regulated trafficking determinant for CD8 (a model transmembrane protein) using fluorescent-activated cell sorting analysis and, using green fluorescent protein-tagged alpha1C subunits expressed in cultured hippocampal neurons, that Ca2+/CaM interaction with this domain accelerated trafficking of Ca(V)1.2 channels to distal regions of the dendritic arbor. Furthermore, this Ca2+/CaM-accelerated trafficking was activity dependent. Thus, CaM imparts Ca2+-dependent regulation not only to mature Ca(V)1.2 channels at the cell surface but also to steps during channel biosynthesis.}, address = {Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.}, author = {Wang, H. G. and George, M. S. and Kim, J. and Wang, C. and Pitt, G. S. }, citeulike-article-id = {2425890}, doi = {10.1523/JNEUROSCI.1720-07.2007}, issn = {1529-2401}, journal = {J Neurosci}, keywords = {calmodulin, cultured\_hippo\_neurons, ion\_channels, trafficking}, month = {August}, number = {34}, pages = {9086--9093}, posted-at = {2008-02-25 15:55:21}, priority = {0}, title = {Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.1720-07.2007}, volume = {27}, year = {2007} }

TY - JOUR ID - citeulike:2425890 L3 - citeulike-article-id:2425890 TI - Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons. JF - J Neurosci VL - 27 IS - 34 SP - 9086 EP - 9093 AD - Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. SN - 1529-2401 N2 - As the Ca2+-sensor for Ca2+-dependent inactivation, calmodulin (CaM) has been proposed, but never definitively demonstrated, to be a constitutive Ca(V)1.2 Ca2+ channel subunit. Here we show that CaM is associated with the Ca(V)1.2 pore-forming alpha1C subunit in brain in a Ca2+-independent manner. Within its CaM binding pocket, alpha1C has been proposed to contain a membrane targeting domain. Because ion channel subunits assemble early during channel biosynthesis, we postulated that this association with CaM could afford the opportunity for Ca2+-dependent regulation of membrane targeting. We showed that the isolated domain functioned as a Ca2+/CaM regulated trafficking determinant for CD8 (a model transmembrane protein) using fluorescent-activated cell sorting analysis and, using green fluorescent protein-tagged alpha1C subunits expressed in cultured hippocampal neurons, that Ca2+/CaM interaction with this domain accelerated trafficking of Ca(V)1.2 channels to distal regions of the dendritic arbor. Furthermore, this Ca2+/CaM-accelerated trafficking was activity dependent. Thus, CaM imparts Ca2+-dependent regulation not only to mature Ca(V)1.2 channels at the cell surface but also to steps during channel biosynthesis. KW - calmodulin KW - cultured_hippo_neurons KW - ion_channels KW - trafficking AU - Wang, HG AU - George, MS AU - Kim, J AU - Wang, C AU - Pitt, GS PY - 2007/08/22/ UR - http://dx.doi.org/10.1523/JNEUROSCI.1720-07.2007 ER -