Muraro, Nara I., Weston, Andrew J., Gerber, Andre P., Luschnig, Stefan, Moffat, Kevin G. and Baines, Richard A.. (2008) Pumilio binds para mRNA and requires nanos and brat to regulate sodium current in drosophila motoneurons. Journal of Neuroscience, Vol.28 (No.9). pp. 2099-2109. ISSN 0270-6474

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Abstract

Homeostatic regulation of ionic currents is of paramount importance during periods of synaptic growth or remodeling. Our previous work has identified the translational repressor Pumilio (Pum) as a regulator of sodium current (INa) and excitability in Drosophila motoneurons. In this current study, we show that Pum is able to bind directly the mRNA encoding the Drosophila voltage-gated sodium channel paralytic (para). We identify a putative binding site for Pum in the 3' end of the para open reading frame (ORF). Characterization of the mechanism of action of Pum, using whole-cell patch clamp and real-time reverse transcription-PCR, reveals that the full-length protein is required for translational repression of para mRNA. Additionally, the cofactor Nanos is essential for Pum-dependent para repression, whereas the requirement for Brain Tumor (Brat) is cell type specific. Thus, Pum-dependent regulation of INa in motoneurons requires both Nanos and Brat, whereas regulation in other neuronal types seemingly requires only Nanos but not Brat. We also show that Pum is able to reduce the level of nanos mRNA and as such identify a potential negative-feedback mechanism to protect neurons from overactivity of Pum. Finally, we show coupling between INa (para) and IK (Shal) such that Pum-mediated change in para results in a compensatory change in Shal. The identification of para as a direct target of Pum represents the first ion channel to be translationally regulated by this repressor and the location of the binding motif is the first example in an ORF rather than in the canonical 3'-untranslated region of target transcripts.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Drosophila melanogaster, Synapses, Ion-permeable membranes, Motor neurons
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date:	27 February 2008
Volume:	Vol.28
Number:	No.9
Page Range:	pp. 2099-2109
Identification Number:	10.1523/JNEUROSCI.5092-07.2008
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England), Human Frontiers Science Program (HFSP)
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URI:	http://wrap.warwick.ac.uk/id/eprint/669

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