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Published April 29, 2009 | Published
Journal Article Open

The translational repressors Nanos and Pumilio have divergent effects on presynaptic terminal growth and postsynaptic glutamate receptor subunit composition


Pumilio (Pum) is a translational repressor that binds selectively to target mRNAs and recruits Nanos (Nos) as a corepressor. In the larval neuromuscular system, Pum represses expression of the translation factor eIF-4E and the glutamate receptor subunit GluRIIA. Here, we show that Nos, like Pum, is expressed at the neuromuscular junction (NMJ) and in neuronal cell bodies. Surprisingly, however, Nos and Pum have divergent functions on both the presynaptic and postsynaptic sides of the NMJ. In nos mutant and nos RNA interference larvae, the number of NMJ boutons is increased, whereas loss of Pum reduces the bouton number. On the postsynaptic side, Nos acts in opposition to Pum in regulating the subunit composition of the glutamate receptor. NMJ active zones are associated with GluRIIA- and GluRIIB-containing receptor clusters. Loss of Nos causes downregulation of GluRIIA and increases the levels of GluRIIB. Consistent with this finding, the electrophysiological properties of NMJs lacking postsynaptic Nos suggest that they use primarily GluRIIB-containing receptors. Nos can regulate GluRIIB in the absence of GluRIIA, suggesting that the effects of Nos on GluRIIB levels are at least partially independent of synaptic competition between GluRIIA and GluRIIB. Nos is a target for Pum repression, and Pum binds selectively to the 3' untranslated regions of the nos and GluRIIA mRNAs. Our results suggest a model in which regulatory interplay among Pum, Nos, GluRIIA, and GluRIIB could cause a small change in Pum activity to be amplified into a large shift in the balance between GluRIIA and GluRIIB synapses.

Additional Information

© Society for Neuroscience. For the first six months after publication SfN's license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license https://creativecommons.org/licenses/by/4.0/). Received Jan. 31, 2009; revised Feb. 27, 2009; accepted March 20, 2009. This work was supported by National Institutes of Health Grants RO1 NS28182 (K.Z.) and GM061107 (E.R.G.). We thank Anna Salazar for comments on this manuscript and Ed Silverman (Zinn laboratory) for making Nos protein that was used for antibody generation. We thank Christoph Schuster for pointing out that the minis in our traces for nos mutants had a faster decay rate. We thank Aaron DiAntonio and Stephan Sigrist for helpful advice. We thank Thomas Osterwalder and Haig Keshishian for the muscle GeneSwitch line on the second chromosome, Brett Burke and Haig Keshishian for OK6-GAL4, Vivian Budnik for C57-GAL4, Paul Macdonald for rat Nanos antibody; Peter Bryant for Discs-Large antibody, and Aaron DiAntonio for GluRIIB antibody. We thank Susan Ou of the Caltech Monoclonal Antibody Facility for generating the Nos antibody and the DSHB for synapsin and GluRIIA antibodies. We thank Elena Armand for help with maintaining fly lines. We thank Erin Schuman for the use of her Zeiss LSM510 confocal microscope and Chin-Yin Tai (Schuman laboratory) for advice on quantitation of glutamate receptor puncta. We thank Viola Nesterova for extensive help with figure preparation. Last, we thank anonymous reviewers for comments that greatly improved this manuscript.

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