QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 22, 2007, 27(34):9086-9093; doi:10.1523/JNEUROSCI.1720-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Wang, H.-G. Articles by Pitt, G. S. Search for Related Content PubMed PubMed Citation Articles by Wang, H.-G. Articles by Pitt, G. S.

 Previous Article  |  Next Article 

Cellular/Molecular
Ca²⁺/Calmodulin Regulates Trafficking of Ca_V1.2 Ca²⁺ Channels in Cultured Hippocampal Neurons

Hong-Gang Wang,^1 * Meena S. George,^3 * James Kim,¹ Chaojian Wang,¹ and Geoffrey S. Pitt^1,2

Departments of ¹Pharmacology and ²Medicine, Division of Cardiology, ³Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032

Correspondence should be addressed to Geoffrey S. Pitt, Department of Medicine, Duke University Medical Center, Durham, NC 27710. Email: geoffrey.pitt{at}duke.edu

As the Ca²⁺-sensor for Ca²⁺-dependent inactivation, calmodulin (CaM) has been proposed, but never definitively demonstrated, to be a constitutive Ca_V1.2 Ca²⁺ channel subunit. Here we show that CaM is associated with the Ca_V1.2 pore-forming _1C subunit in brain in a Ca²⁺-independent manner. Within its CaM binding pocket, _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 _1C subunits expressed in cultured hippocampal neurons, that Ca²⁺/CaM interaction with this domain accelerated trafficking of Ca_V1.2 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_V1.2 channels at the cell surface but also to steps during channel biosynthesis.

Key words: calcium; calcium channels; calmodulin; channel; hippocampus; trafficking

---

Received Dec. 30, 2006; revised July 9, 2007; accepted July 9, 2007.

Correspondence should be addressed to Geoffrey S. Pitt, Department of Medicine, Duke University Medical Center, Durham, NC 27710. Email: geoffrey.pitt{at}duke.edu

This article has been cited by other articles:

				S. Levy, O. Beharier, Y. Etzion, M. Mor, L. Buzaglo, L. Shaltiel, L. A. Gheber, J. Kahn, A. J. Muslin, A. Katz, et al. Molecular Basis for Zinc Transporter 1 Action as an Endogenous Inhibitor of L-type Calcium Channels J. Biol. Chem., November 20, 2009; 284(47): 32434 - 32443. [Abstract] [Full Text] [PDF]

				K. Griessmeier, H. Cuny, K. Rotzer, O. Griesbeck, H. Harz, M. Biel, and C. Wahl-Schott Calmodulin Is a Functional Regulator of Cav1.4 L-type Ca2+ Channels J. Biol. Chem., October 23, 2009; 284(43): 29809 - 29816. [Abstract] [Full Text] [PDF]

				X. Xu and H. M. Colecraft Engineering Proteins for Custom Inhibition of CaV Channels Physiology, August 1, 2009; 24(4): 210 - 218. [Abstract] [Full Text] [PDF]

				H. Vacher, D. P. Mohapatra, and J. S. Trimmer Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons Physiol Rev, October 1, 2008; 88(4): 1407 - 1447. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help