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Mol Cell Neurosci
2022 Dec 01;123:103772. doi: 10.1016/j.mcn.2022.103772.
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Signal amplification in growth cone gradient sensing by a double negative feedback loop among PTEN, PI(3,4,5)P3 and actomyosin.
Li X, Shim S, Hardin KR, Vanaja KG, Song H, Levchenko A, Ming GL, Zheng JQ.
???displayArticle.abstract??? Axon guidance during neural wiring involves a series of precisely controlled chemotactic events by the motile axonal tip, the growth cone. A fundamental question is how neuronal growth cones make directional decisions in response to extremely shallow gradients of guidance cues with exquisite sensitivity. Here we report that nerve growth cones possess a signal amplification mechanism during gradient sensing process. In neuronal growth cones of Xenopus spinal neurons, phosphatidylinositol-3,4,5-trisphosphate (PIP3), an important signaling molecule in chemotaxis, was actively recruited to the up-gradient side in response to an external gradient of brain-derived neurotrophic factor (BDNF), resulting in an intracellular gradient with approximate 30-fold amplification of the input. Furthermore, a reverse gradient of phosphatase and tensin homolog (PTEN) was induced by BDNF within the growth cone and the increased PTEN activity at the down-gradient side is required for the amplification of PIP3 signals. Mechanistically, the establishment of both positive PIP3 and reverse PTEN gradients depends on the filamentous actin network. Together with computational modeling, our results revealed a double negative feedback loop among PTEN, PIP3 and actomyosin for signal amplification, which is essential for gradient sensing of neuronal growth cones in response to diffusible cues.
Akiyama,
Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals.
2009, Pubmed
Akiyama,
Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals.
2009,
Pubmed Bellon,
Keeping up with advances in axon guidance.
2018,
Pubmed Bouzigues,
Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging.
2007,
Pubmed Burkel,
Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin.
2007,
Pubmed
,
Xenbase Gomez,
Actin dynamics in growth cone motility and navigation.
2014,
Pubmed Guy,
Lipids as new players in axon guidance and circuit development.
2021,
Pubmed Henle,
Asymmetric PI(3,4,5)P3 and Akt signaling mediates chemotaxis of axonal growth cones.
2011,
Pubmed
,
Xenbase Hevroni,
Hippocampal plasticity involves extensive gene induction and multiple cellular mechanisms.
1998,
Pubmed Iijima,
Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
2002,
Pubmed Janetopoulos,
Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton.
2004,
Pubmed Jin,
Gradient sensing during chemotaxis.
2013,
Pubmed Joanne Wang,
A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues.
2008,
Pubmed
,
Xenbase Kerstein,
Mechanochemical regulation of growth cone motility.
2015,
Pubmed Kolodkin,
Mechanisms and molecules of neuronal wiring: a primer.
2011,
Pubmed Kölsch,
The regulation of cell motility and chemotaxis by phospholipid signaling.
2008,
Pubmed Kovács,
Mechanism of blebbistatin inhibition of myosin II.
2004,
Pubmed Leung,
Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1.
2006,
Pubmed
,
Xenbase Levchenko,
Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils.
2002,
Pubmed Lohof,
Asymmetric modulation of cytosolic cAMP activity induces growth cone turning.
1992,
Pubmed
,
Xenbase Mai,
Axon initiation and growth cone turning on bound protein gradients.
2009,
Pubmed Meili,
Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.
1999,
Pubmed Ming,
Acute morphogenic and chemotropic effects of neurotrophins on cultured embryonic Xenopus spinal neurons.
1997,
Pubmed
,
Xenbase Ming,
Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance.
1999,
Pubmed
,
Xenbase Ostap,
2,3-Butanedione monoxime (BDM) as a myosin inhibitor.
2002,
Pubmed Parent,
A cell's sense of direction.
1999,
Pubmed Quinn,
CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin.
2008,
Pubmed Rosoff,
A new chemotaxis assay shows the extreme sensitivity of axons to molecular gradients.
2004,
Pubmed Sánchez-Huertas,
With the Permission of Microtubules: An Updated Overview on Microtubule Function During Axon Pathfinding.
2021,
Pubmed Schaefer,
Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones.
2002,
Pubmed Schmid,
Bisperoxovanadium compounds are potent PTEN inhibitors.
2004,
Pubmed SenGupta,
The principles of directed cell migration.
2021,
Pubmed Servant,
Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
2000,
Pubmed Shim,
XTRPC1-dependent chemotropic guidance of neuronal growth cones.
2005,
Pubmed
,
Xenbase Short,
Cell adhesion and invasion mechanisms that guide developing axons.
2016,
Pubmed Sloan,
Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.
2015,
Pubmed Sourjik,
Receptor clustering and signal processing in E. coli chemotaxis.
2004,
Pubmed Sun,
PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway.
1999,
Pubmed Tessier-Lavigne,
The molecular biology of axon guidance.
1996,
Pubmed Tojima,
Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone.
2007,
Pubmed Tu,
Quantitative modeling of bacterial chemotaxis: signal amplification and accurate adaptation.
2013,
Pubmed van Diepen,
MyosinV controls PTEN function and neuronal cell size.
2009,
Pubmed Vitriol,
Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane.
2012,
Pubmed Wang,
Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils.
2002,
Pubmed Xu,
Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils.
2003,
Pubmed Yao,
An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance.
2006,
Pubmed
,
Xenbase Zang,
New insights into the molecular mechanisms of axon guidance receptor regulation and signaling.
2021,
Pubmed Zheng,
Turning of nerve growth cones induced by neurotransmitters.
1994,
Pubmed
,
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