ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
PHR regulates growth cone pausing at intermediate targets through microtubule disassembly.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- UNC-116 and UNC-16 function with the NEKL-3 kinase to promote axon targeting.Development (Cambridge, England) · 2023Article
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- The Ubiquitinated Axon: Local Control of Axon Development and Function by Ubiquitin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Chemotherapy-Induced Peripheral Neuropathy and Changes in Cytoskeleton.International journal of molecular sciences · 2019Review
- XMAP215 promotes microtubule-F-actin interactions to regulate growth cone microtubules during axon guidance inJournal of cell science · 2019Article
- Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub.eLife · 2019Article
- Tubulin Polymerization Promoting Protein, Ringmaker, and MAP1B Homolog Futsch Coordinate Microtubule Organization and Synaptic Growth.Frontiers in cellular neuroscience · 2019Article
- The ubiquitin ligase PHR promotes directional regrowth of spinal zebrafish axons.Communications biology · 2019Article
- RPM-1 and DLK-1 regulate pioneer axon outgrowth by controlling Wnt signaling.Development (Cambridge, England) · 2018Article
- Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics.The Journal of cell biology · 2018Article
- RPM-1 regulates axon termination by affecting growth cone collapse and microtubule stability.Development (Cambridge, England) · 2017Article
- Wallenda/DLK protein levels are temporally downregulated by Tramtrack69 to allow R7 growth cones to become stationary boutons.Development (Cambridge, England) · 2016Article
- Kif1B Interacts with KBP to Promote Axon Elongation by Localizing a Microtubule Regulator to Growth Cones.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The PHR proteins: intracellular signaling hubs in neuronal development and axon degeneration.Neural development · 2016Review
- Neurodegeneration and microtubule dynamics: death by a thousand cuts.Frontiers in cellular neuroscience · 2015Review
- Regulation of intrinsic axon growth ability at retinal ganglion cell growth cones.Investigative ophthalmology & visual science · 2014Article
- RPM-1 is localized to distinct subcellular compartments and regulates axon length in GABAergic motor neurons.Neural development · 2014Article
- RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development.PLoS genetics · 2014Article
- Different modes of growth cone collapse in NG 108-15 cells.European biophysics journal : EBJ · 2013Article
- The role of ubiquitin-mediated pathways in regulating synaptic development, axonal degeneration and regeneration: insights from fly and worm.The Journal of physiology · 2013Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal growth cones use intermediate targets to navigate in the developing nervous system. Encountering these sites is correlated with growth cone pausing. PHR (Phr1, Esrom, Highwire, RPM-1) is a large neuronal ubiquitin ligase that interacts with multiple signaling pathways. Mouse and zebrafish phr mutants have highly penetrant axon pathfinding defects at intermediate targets. Mouse phr mutants contain excessive microtubules in the growth cone, which has been attributed to upregulation of DLK/p38 signaling. Here, we ask whether this pathway and microtubule misregulation are indeed linked to guidance errors in the vertebrate brain, using the zebrafish. By live imaging, we show that loops form when microtubules retract without depolymerizing. JNK, but not p38, phosphorylation is increased in mutant growth cones. However microtubule looping cannot be suppressed by inhibiting JNK. The phr microtubule defect can be phenocopied by taxol, while microtubule destabilization in vitro using nocodazole prevents loop formation. Acute disruption in vivo with nocodazole suppresses the intermediate target guidance defect. Given that microtubule looping is associated with growth cone pausing, we propose that microtubule disassembly, mediated by PHR, is essential for exiting the paused state at intermediate targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.