title: Staufen targets coracle mRNA to Drosophila neuromuscular junctions and regulates GluRIIA synaptic accumulation and bouton number.
abstract: The post-synaptic translation of localised mRNAs has been postulated to underlie several forms of plasticity at vertebrate synapses, but the mechanisms that target mRNAs to these postsynaptic sites are not well understood. Here we show that the evolutionary conserved dsRNA binding protein, Staufen, localises to the postsynaptic side of the Drosophila neuromuscular junction (NMJ), where it is required for the localisation of coracle mRNA and protein. Staufen plays a well-characterised role in the localisation of oskar mRNA to the oocyte posterior, where Staufen dsRNA-binding domain 5 is specifically required for its translation. Removal of Staufen dsRNA-binding domain 5, disrupts the postsynaptic accumulation of Coracle protein without affecting the localisation of cora mRNA, suggesting that Staufen similarly regulates Coracle translation. Tropomyosin II, which functions with Staufen in oskar mRNA localisation, is also required for coracle mRNA localisation, suggesting that similar mechanisms target mRNAs to the NMJ and the oocyte posterior. Coracle, the orthologue of vertebrate band 4.1, functions in the anchoring of the glutamate receptor IIA subunit (GluRIIA) at the synapse. Consistent with this, staufen mutant larvae show reduced accumulation of GluRIIA at synapses. The NMJs of staufen mutant larvae have also a reduced number of synaptic boutons. Altogether, this suggests that this novel Staufen-dependent mRNA localisation and local translation pathway may play a role in the developmentally regulated growth of the NMJ.
authors.affiliation: The WellcomeCRUK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gardiol
authors.affiliation: The WellcomeCRUK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, United Kingdom. Electronic address: d.stjohnston@gurdon.cam.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: St Johnston
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004330:Drosophila / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017470:Receptors, Glutamate; C442474:cora protein, Drosophila; C069927:stau protein, Drosophila
keywords: Glutamate receptors; Neuromuscular junction; Staufen; Subsynaptic translation; mRNA localisation