title: The conserved P body component HPat/Pat1 negatively regulates synaptic terminal growth at the larval Drosophila neuromuscular junction.
abstract: The temporal and spatial regulation of protein synthesis plays an important role in the control of neural physiology. In axons and dendrites, translationally repressed mRNAs are actively transported to their destinations in a variety of ribonucleoprotein particles (RNPs). A subset of these neuronal RNPs has been shown to contain proteins associated with mRNA processing bodies (P bodies). P bodies are a class of highly conserved cytoplasmic granules that have been linked to both mRNA decay and translational repression via general and miRNA-mediated pathways. Here, we characterize functions for HPat/Pat1 (also known as Patr-1), a core component of P bodies, at the glutamatergic larval Drosophila neuromuscular junction (NMJ). We show that hpat mutants exhibit a strong synaptic hyperplasia at the NMJ. The synaptic defects observed in hpat mutants are associated with rearrangement of the axonal microtubule cytoskeleton suggesting that HPat negatively regulates presynaptic microtubule-based growth during NMJ development. Consistent with this, overexpression of HPat also blocks the rapid growth of presynaptic boutons induced by spaced depolarization. Finally, we demonstrate that HPat interacts genetically with the catalytic subunit of the deadenylase complex (twin/CCR4) and the miRNA pathway (Argonaute 1) to control bouton formation. We propose that HPat is required to target mRNAs involved in the control of microtubule architecture and synaptic terminal growth for repression, presumably in P bodies, via both general and miRNA-mediated mechanisms.
authors.affiliation: Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, Denver, CO 80208, USA.
authors.forename: Sarala J
authors.initials: SJ
authors.lastname: Pradhan
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Nesler
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Rosen
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Mani
authors.initials: M
authors.lastname: Ramaswami
authors.forename: Scott A
authors.initials: SA
authors.lastname: Barbee
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C551546:PAT1 protein, Drosophila; C549399:Patr-1 protein, Drosophila; D016601:RNA-Binding Proteins