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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 15, 2008, 28(42):10604-10617; doi:10.1523/JNEUROSCI.2709-08.2008

This Article Free Access Article Free Access Article Full Text Full Text (PDF) Supplemental Data 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 Related articles in J. Neurosci. 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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Ferron, L. Articles by Dolphin, A. C. Search for Related Content PubMed PubMed Citation Articles by Ferron, L. Articles by Dolphin, A. C.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Stargazin-Related Protein 7 Interacts with the mRNA-Binding Protein Heterogeneous Nuclear Ribonucleoprotein A2 and Regulates the Stability of Specific mRNAs, Including Ca_V2.2

Laurent Ferron, Anthony Davies, Karen M. Page, David J. Cox, Jerôme Leroy, Dominic Waithe, Adrian J. Butcher, Priya Sellaturay, Steven Bolsover, Wendy S. Pratt, Fraser J. Moss, and Annette C. Dolphin

Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to Annette C. Dolphin, Laboratory of Cellular and Molecular Neuroscience, Andrew Huxley Building, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.dolphin{at}ucl.ac.uk

The role(s) of the novel stargazin-like -subunit proteins remain controversial. We have shown previously that the neuron-specific 7 suppresses the expression of certain calcium channels, particularly Ca_V2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of 7 on Ca_V2.2 expression is via an increase in the degradation rate of Ca_V2.2 mRNA and hence a reduction of Ca_V2.2 protein level. Furthermore, exogenous expression of 7 in PC12 cells also decreased the endogenous Ca_V2.2 mRNA level. Conversely, knockdown of endogenous 7 with short-hairpin RNAs produced a reciprocal enhancement of Ca_V2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed 7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C terminus of 7 is essential for all its effects, and we show that 7 binds directly via its C terminus to a heterogeneous nuclear ribonucleoprotein (hnRNP A2), which also binds to a motif in Ca_V2.2 mRNA, and is associated with native Ca_V2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances Ca_V2.2 I_Ba, and this enhancement is prevented by a concentration of 7 that alone has no effect on I_Ba. The effect of 7 is selective for certain mRNAs because it had no effect on 2-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride cotransporter, KCC1, which contains a similar hnRNP A2 binding motif to that in Ca_V2.2 mRNA. Our results indicate that 7 plays a role in stabilizing Ca_V2.2 mRNA.

Key words: N-type; calcium channel; mRNA stability; 7 subunit; hnRNP A2; stargazin

---

Received June 13, 2008; revised Aug. 22, 2008; accepted Sept. 2, 2008.

Correspondence should be addressed to Annette C. Dolphin, Laboratory of Cellular and Molecular Neuroscience, Andrew Huxley Building, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.dolphin{at}ucl.ac.uk

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2008 28: i. [Full Text]  

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help