Dendritic Localization of the Translational Repressor Pumilio 2 and Its Contribution to Dendritic Stress Granules

Vessey, John P.; Vaccani, Angelo; Xie, Yunyun; Dahm, Ralf; Karra, Daniela; Kiebler, Michael; Macchi, Paolo

doi:10.1523/jneurosci.0649-06.2006

Cited by 167 publications

(184 citation statements)

References 54 publications

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“…Because microRNAs exert their effects on mRNAs in processing bodies (P-bodies) or RNA-induced silencing complexes (RISCs) (Anderson and Kedersha, 2006;Parker and Sheth, 2007), this finding suggested that RISC and specifically P-bodies might be involved in this process. We have detected P-bodies in neurons, both in the cell body and in dendrites (Vessey et al, 2006). Furthermore, a recent study reported that P-body (DCP1a, Rck/p54/ DDX6) and transport RNP [FMRP (fragile X mental retardation protein), Staufen (Stau)] markers colocalize in dendrites of Drosophila olfactory neurons (Barbee et al, 2006), raising the possi-bility that P-body components contribute to the translational silencing and/or turnover of dendritically localized mRNAs.…”

Section: Introductionmentioning

confidence: 79%

Dynamic Interaction between P-Bodies and Transport Ribonucleoprotein Particles in Dendrites of Mature Hippocampal Neurons

Zeitelhofer

Karra²,

Macchi³

et al. 2008

J. Neurosci.

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125

129

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The dendritic localization of mRNAs and their subsequent translation at stimulated synapses contributes to the experience-dependent remodeling of synapses and thereby to the establishment of long-term memory. Localized mRNAs are transported in a translationally silent manner to distal dendrites in specific ribonucleoprotein particles (RNPs), termed transport RNPs. A recent study suggested that processing bodies (P-bodies), which have recently been identified as sites of RNA degradation and translational control in eukaryotic cells, may participate in the translational control of dendritically localized mRNAs in Drosophila neurons. This study raised the interesting question of whether dendritic transport RNPs are distinct from P-bodies or whether those structures share significant overlap in their molecular composition in mammalian neurons. Here, we show that P-body and transport RNP markers do not colocalize and are not transported together in the same particles in dendrites of mammalian neurons. Detailed time-lapse videomicroscopy analyses reveal, however, that both P-bodies and transport RNPs can interact in a dynamic manner via docking. Docking is a frequent event involving as much as 50% of all dendritic P-bodies. Chemically induced neuronal activity results in a 60% decrease in the number of P-bodies in dendrites, suggesting that P-bodies disassemble after synaptic stimulation. Our data lend support to the exciting hypothesis that dendritically localized mRNAs might be stored in P-bodies and be released and possibly translated when synapses become activated.

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Section: Introductionmentioning

confidence: 79%

Dynamic Interaction between P-Bodies and Transport Ribonucleoprotein Particles in Dendrites of Mature Hippocampal Neurons

Zeitelhofer

Karra²,

Macchi³

et al. 2008

J. Neurosci.

Self Cite

125

129

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“…We tested this hypothesis using shRNA to down-regulate and a Pum2-EYFP fusion protein to overexpress Pum2, respectively. The efficiency of shRNA-mediated Pum2 (shPum2) down-regulation in dissociated hippocampal neurons has been previously demonstrated (7,12). Hippocampal neurons were transiently transfected at 7 days in vitro (DIV), fixed 3 days later, and subjected to Sholl analysis (13).…”

Section: Resultsmentioning

confidence: 99%

“…For details of all constructs, cloning, and antibodies, see SI Methods. Rat hippocampal neurons were cultured and transiently transfected as described (7,24,25).…”

Section: Methodsmentioning

confidence: 99%

“…Finally, loss of pumilio impairs long-term memory (6). A homolog of Pum, mammalian Pum2, is expressed in hippocampal neurons and is found in ribonucleoparticles (RNPs) in the somatodendritic compartment (7). Its punctate microtubule-associated expression pattern in dendrites mimics that of RNA-binding proteins (RBPs) known to be involved in RNA transport and translational control (8,9).…”

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confidence: 99%

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Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function

Vessey¹,

Schoderboeck²,

Gingl

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

121

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In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNAcontaining particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control.

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“…The possibility of PUM2 being involved in this capacity is not unlikely. It will be interesting to determine whether PUM2 binds to the AChE mRNA in CNS neurons because PUM2 is expressed by neurons and is involved in the formation of stress granules in dendrites (17,22). AChE is highly expressed in cholinergic neurons and their targets in the CNS and specifically in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Translational Regulation of Acetylcholinesterase by the RNA-binding Protein Pumilio-2 at the Neuromuscular Synapse

Marrero

Rossi

Darr

et al. 2011

Journal of Biological Chemistry

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Background: Acetylcholinesterase RNA and protein are concentrated at the neuromuscular synapse but how its translation is regulated is not known. Results: The translational repressor Pumilio-2 is localized at the neuromuscular synapse where it binds acetylcholinesterase mRNA. Conclusions: Pumilio-2 regulates acetylcholinesterase expression at the neuromuscular synapse. Significance: Translational control of synaptic proteins can regulate synaptic transmission; changing acetylcholinesterase levels could influence sensitivity of cholinergic synapses.

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Dendritic Localization of the Translational Repressor Pumilio 2 and Its Contribution to Dendritic Stress Granules

Cited by 167 publications

References 54 publications

Dynamic Interaction between P-Bodies and Transport Ribonucleoprotein Particles in Dendrites of Mature Hippocampal Neurons

Dynamic Interaction between P-Bodies and Transport Ribonucleoprotein Particles in Dendrites of Mature Hippocampal Neurons

Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function

Translational Regulation of Acetylcholinesterase by the RNA-binding Protein Pumilio-2 at the Neuromuscular Synapse

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