Continuously Tunable Ca2+ Regulation of RNA-Edited CaV1.3 Channels

Hojjat Bazzazi, Manu BenJohny, Paul J. Adams, Tuck Wah Soong, David T. Yue

Research output: Contribution to journalArticle

Abstract

CaV1.3 ion channels are dominant Ca2+ portals into pacemaking neurons, residing at the epicenter of brain rhythmicity and neurodegeneration. Negative Ca2+ feedback regulation of CaV1.3 channels (CDI) is therefore critical for Ca2+ homeostasis. Intriguingly, nearly half the CaV1.3 transcripts in the brainare RNA edited to reduce CDI and influence oscillatory activity. It is then mechanistically remarkable that this editing occurs precisely within an IQdomain, whose interaction with Ca2+-bound calmodulin (Ca2+/CaM) is believed to induce CDI. Here, we sought the mechanism underlying the altered CDI of edited channels. Unexpectedly, editing failed to attenuate Ca2+/CaM binding. Instead, editing weakened the prebinding of Ca2+-free CaM (apoCaM) to channels, which proves essential for CDI. Thus, editing might render CDI continuously tunable by fluctuations in ambient CaM, a prominent effect we substantiate in substantia nigral neurons. This adjustability of Ca2+ regulation by CaM now looms as a key element of CNS Ca2+ homeostasis

Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalCell Reports
Volume5
Issue number2
DOIs
StatePublished - Oct 11 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Continuously Tunable Ca<sup>2+</sup> Regulation of RNA-Edited Ca<sub>V</sub>1.3 Channels'. Together they form a unique fingerprint.

  • Cite this

    Bazzazi, H., BenJohny, M., Adams, P. J., Soong, T. W., & Yue, D. T. (2013). Continuously Tunable Ca2+ Regulation of RNA-Edited CaV1.3 Channels. Cell Reports, 5(2), 367-377. https://doi.org/10.1016/j.celrep.2013.09.006