title: Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex.
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-binding 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 translation 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.
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Nils
authors.initials: N
authors.lastname: Hadziselimovic
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Vanja
authors.initials: V
authors.lastname: Vukojevic
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Peter
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Milnik
authors.affiliation: Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fastenrath
authors.affiliation: Department of Medical Chemistry, Semmelweis University, Tűzoltó u. 37-47, 1094 Budapest, Hungary.
authors.forename: Bank Gabor
authors.initials: BG
authors.lastname: Fenyves
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Hieber
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Demougin
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Vogler
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland.
authors.forename: Dominique J-F
authors.initials: DJ
authors.lastname: de Quervain
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.affiliation: Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland. Electronic address: a.stetak@unibas.ch.
authors.forename: Attila
authors.initials: A
authors.lastname: Stetak
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics* / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008568:Memory; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D018510:RNA, Helminth / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013569:Synapses
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D018510:RNA, Helminth; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C491299:msi-1 protein, C elegans