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Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex

Hadziselimovic, Nils and Vukojevic, Vanja and Peter, Fabian and Milnik, Annette and Fastenrath, Matthias and Fenyves, Bank Gabor and Hieber, Petra and Demougin, Philippe and Vogler, Christian and de Quervain, Dominique J.-F. and Papassotiropoulos, Andreas and Stetak, Attila. (2014) Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex. Cell, Vol. 156, H. 6. pp. 1153-1166.

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Official URL: http://edoc.unibas.ch/dok/A6243377

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Abstract

A plastic nervous system requires the ability not only to acquire and store but also to forget. Here, we report that musashi (msi-1) is necessary for time- dependent memory loss in C. elegans. Tissue- specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-bind- ing protein immunoprecipitation (IP), we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2, and ARX-3 trans- lation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning-induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology
07 Faculty of Psychology > Departement Psychologie > Ehemalige Einheiten Psychologie > Molecular Neuroscience (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas and Vogler, Christian and de Quervain, Dominique J.-F. and Fastenrath, Matthias and Vukojevic, Vanja and Milnik, Annette and Stetak, Attila
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:23 May 2014 08:33

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