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

Publication ,  Journal Article
Wang, H-G; George, MS; Kim, J; Wang, C; Pitt, GS
Published in: J Neurosci
August 22, 2007

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.

Duke Scholars

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

August 22, 2007

Volume

27

Issue

34

Start / End Page

9086 / 9093

Location

United States

Related Subject Headings

  • Transfection
  • Rats, Sprague-Dawley
  • Rats
  • Protein Transport
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Models, Biological
  • Immunoprecipitation
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, H.-G., George, M. S., Kim, J., Wang, C., & Pitt, G. S. (2007). Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons. J Neurosci, 27(34), 9086–9093. https://doi.org/10.1523/JNEUROSCI.1720-07.2007
Wang, Hong-Gang, Meena S. George, James Kim, Chaojian Wang, and Geoffrey S. Pitt. “Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons.J Neurosci 27, no. 34 (August 22, 2007): 9086–93. https://doi.org/10.1523/JNEUROSCI.1720-07.2007.
Wang H-G, George MS, Kim J, Wang C, Pitt GS. Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons. J Neurosci. 2007 Aug 22;27(34):9086–93.
Wang, Hong-Gang, et al. “Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons.J Neurosci, vol. 27, no. 34, Aug. 2007, pp. 9086–93. Pubmed, doi:10.1523/JNEUROSCI.1720-07.2007.
Wang H-G, George MS, Kim J, Wang C, Pitt GS. Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neurons. J Neurosci. 2007 Aug 22;27(34):9086–9093.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

August 22, 2007

Volume

27

Issue

34

Start / End Page

9086 / 9093

Location

United States

Related Subject Headings

  • Transfection
  • Rats, Sprague-Dawley
  • Rats
  • Protein Transport
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Models, Biological
  • Immunoprecipitation
  • Humans