ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Asymmetric PI(3,4,5)P3 and Akt signaling mediates chemotaxis of axonal growth cones.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Integrin-mediated electric axon guidance underlying optic nerve formation in the embryonic chick retina.Communications biology · 2023Article
- Signal amplification in growth cone gradient sensing by a double negative feedback loop among PTEN, PI(3,4,5)PMolecular and cellular neurosciences · 2022Article
- Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling.Neural regeneration research · 2022Review
- Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer's disease.Cell communication and signaling : CCS · 2021Review
- The essential role of primary cilia in cerebral cortical development and disorders.Current topics in developmental biology · 2021Review
- Nystatin Regulates Axonal Extension and Regeneration by Modifying the Levels of Nitric Oxide.Frontiers in molecular neuroscience · 2020Article
- Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models.Developmental cell · 2019Article
- A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways.Neural plasticity · 2019Review
- Phosphoinositides: Regulators of Nervous System Function in Health and Disease.Frontiers in molecular neuroscience · 2019Review
- MicroRNA-21 activation of AktToxicology research · 2016Article
- Inhibition of mTOR sensitizes breast cancer stem cells to radiation-induced repression of self-renewal through the regulation of MnSOD and Akt.International journal of molecular medicine · 2016Article
- Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones.Neural development · 2015Article
- Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells.Chemistry and physics of lipids · 2014Review
- Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission.The Journal of biological chemistry · 2014Article
- Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders.Frontiers in molecular neuroscience · 2014Review
- Differential role of PTEN phosphatase in chemotactic growth cone guidance.The Journal of biological chemistry · 2013Article
- CIP4 coordinates with phospholipids and actin-associated proteins to localize to the protruding edge and produce actin ribs and veils.Journal of cell science · 2013Article
- Primary neuron culture for nerve growth and axon guidance studies in zebrafish (Danio rerio).PloS one · 2013Article
- Optogenetic control of PIP3: PIP3 is sufficient to induce the actin-based active part of growth cones and is regulated via endocytosis.PloS one · 2013Article
- A phosphatidylinositol lipids system, lamellipodin, and Ena/VASP regulate dynamic morphology of multipolar migrating cells in the developing cerebral cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The action of many extracellular guidance cues on axon pathfinding requires Ca2+ influx at the growth cone (Hong et al., 2000; Nishiyama et al., 2003; Henley and Poo, 2004), but how activation of guidance cue receptors leads to opening of plasmalemmal ion channels remains largely unknown. Analogous to the chemotaxis of amoeboid cells (Parent et al., 1998; Servant et al., 2000), we found that a gradient of chemoattractant triggered rapid asymmetric PI(3,4,5)P3 accumulation at the growth cone's leading edge, as detected by the translocation of a GFP-tagged binding domain of Akt in Xenopus laevis spinal neurons. Growth cone chemoattraction required PI(3,4,5)P3 production and Akt activation, and genetic perturbation of polarized Akt activity disrupted axon pathfinding in vitro and in vivo. Furthermore, patch-clamp recording from growth cones revealed that exogenous PI(3,4,5)P3 rapidly activated TRP (transient receptor potential) channels, and asymmetrically applied PI(3,4,5)P3 was sufficient to induce chemoattractive growth cone turning in a manner that required downstream Ca2+ signaling. Thus, asymmetric PI(3,4,5)P3 elevation and Akt activation are early events in growth cone chemotaxis that link receptor activation to TRP channel opening and Ca2+ signaling. Altogether, our findings reveal that PI(3,4,5)P3 elevation polarizes to the growth cone's leading edge and can serve as an early regulator during chemotactic guidance.
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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.