RRC ID 32425
著者 Pradhan SJ, Nesler KR, Rosen SF, Kato Y, Nakamura A, Ramaswami M, Barbee SA.
タイトル The conserved P body component HPat/Pat1 negatively regulates synaptic terminal growth at the larval Drosophila neuromuscular junction.
ジャーナル J Cell Sci
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.
巻・号 125(Pt 24)
ページ 6105-16
公開日 2012-12-15
DOI 10.1242/jcs.113043
PII jcs.113043
PMID 23097047
PMC PMC3585522
MeSH Animals Carrier Proteins / metabolism Carrier Proteins / physiology* Cytoskeleton / genetics Cytoskeleton / metabolism Drosophila / embryology Drosophila / growth & development* Drosophila Proteins / metabolism Drosophila Proteins / physiology* Female Male Neuromuscular Junction / growth & development* Neuromuscular Junction / metabolism Presynaptic Terminals / metabolism Presynaptic Terminals / physiology* RNA-Binding Proteins / metabolism RNA-Binding Proteins / physiology* Synaptic Transmission
IF 4.573
引用数 13
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ DGRC#140728 DGRC#140986 DGRC#200560 DGRC#203904 DGRC#201401