期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 34, 页码 9086-9093出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1720-07.2007
关键词
calcium; calcium channels; calmodulin; channel; hippocampus; trafficking
资金
- NHLBI NIH HHS [R01 HL071165-06A1, R01 HL071165-03, R01 HL071165, R01 HL071165-07, HL 71165, R01 HL071165-05, R01 HL071165-04] Funding Source: Medline
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 alpha(1C) subunit in brain in a Ca2+-independent manner. Within its CaM binding pocket, alpha(1C) 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 alpha(1C) 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.
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