RT Journal Article
SR Electronic
T1 Ca<sup>2+</sup>/Calmodulin Regulates Trafficking of Ca<sub>V</sub>1.2 Ca<sup>2+</sup> Channels in Cultured Hippocampal Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9086
OP 9093
DO 10.1523/JNEUROSCI.1720-07.2007
VO 27
IS 34
A1 Wang, Hong-Gang
A1 George, Meena S.
A1 Kim, James
A1 Wang, Chaojian
A1 Pitt, Geoffrey S.
YR 2007
UL http://www.jneurosci.org/content/27/34/9086.abstract
AB As the Ca2+-sensor for Ca2+-dependent inactivation, calmodulin (CaM) has been proposed, but never definitively demonstrated, to be a constitutive CaV1.2 Ca2+ channel subunit. Here we show that CaM is associated with the CaV1.2 pore-forming α1C subunit in brain in a Ca2+-independent manner. Within its CaM binding pocket, α1C 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 α1C subunits expressed in cultured hippocampal neurons, that Ca2+/CaM interaction with this domain accelerated trafficking of CaV1.2 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 CaV1.2 channels at the cell surface but also to steps during channel biosynthesis.