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J Neurosci
2011 May 11;3119:7016-27. doi: 10.1523/JNEUROSCI.0216-11.2011.
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Asymmetric PI(3,4,5)P3 and Akt signaling mediates chemotaxis of axonal growth cones.
Henle SJ, Wang G, Liang E, Wu M, Poo MM, Henley JR.
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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.
Akiyama,
Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance.
2010, Pubmed
Akiyama,
Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance.
2010,
Pubmed Alessi,
Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase.
1996,
Pubmed Bezzerides,
Rapid vesicular translocation and insertion of TRP channels.
2004,
Pubmed Bobanovic,
Molecular cloning and immunolocalization of a novel vertebrate trp homologue from Xenopus.
1999,
Pubmed
,
Xenbase Brereton,
Evidence that the TRP-1 protein is unlikely to account for store-operated Ca2+ inflow in Xenopus laevis oocytes.
2000,
Pubmed
,
Xenbase Campbell,
Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation.
2001,
Pubmed
,
Xenbase Chadborn,
PTEN couples Sema3A signalling to growth cone collapse.
2006,
Pubmed Chang,
MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin.
2006,
Pubmed Chao,
Neurotrophins and their receptors: a convergence point for many signalling pathways.
2003,
Pubmed Côté,
A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling.
2005,
Pubmed Di Paolo,
Phosphoinositides in cell regulation and membrane dynamics.
2006,
Pubmed Henley,
Guiding neuronal growth cones using Ca2+ signals.
2004,
Pubmed Henley,
Calcium mediates bidirectional growth cone turning induced by myelin-associated glycoprotein.
2004,
Pubmed
,
Xenbase Hong,
Calcium signalling in the guidance of nerve growth by netrin-1.
2000,
Pubmed
,
Xenbase Iijima,
Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
2002,
Pubmed Inoue,
Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration.
2008,
Pubmed Jacinto,
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.
2004,
Pubmed Kennedy,
Axon guidance by diffusible chemoattractants: a gradient of netrin protein in the developing spinal cord.
2006,
Pubmed Kozikowski,
Novel PI analogues selectively block activation of the pro-survival serine/threonine kinase Akt.
2003,
Pubmed Krause,
Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics.
2004,
Pubmed Kwon,
Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6.
2007,
Pubmed Li,
Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor.
2005,
Pubmed
,
Xenbase Markus,
Raf and akt mediate distinct aspects of sensory axon growth.
2002,
Pubmed Ming,
Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance.
1999,
Pubmed
,
Xenbase Moon,
Adjacent pioneer commissural interneuron growth cones switch from contact avoidance to axon fasciculation after midline crossing.
2005,
Pubmed
,
Xenbase Namikawa,
Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration.
2000,
Pubmed Nishikimi,
Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis.
2009,
Pubmed Nishio,
Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1.
2007,
Pubmed Nishiyama,
Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning.
2003,
Pubmed
,
Xenbase Ozaki,
Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers.
2000,
Pubmed Parent,
G protein signaling events are activated at the leading edge of chemotactic cells.
1998,
Pubmed Park,
Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway.
2008,
Pubmed Peng,
Phosphatidylinositol 3-kinase signaling is involved in neurogenesis during Xenopus embryonic development.
2004,
Pubmed
,
Xenbase Potter,
Akt regulates growth by directly phosphorylating Tsc2.
2002,
Pubmed Ramsey,
An introduction to TRP channels.
2006,
Pubmed Ridley,
Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking.
2006,
Pubmed Round,
Netrin signaling leading to directed growth cone steering.
2007,
Pubmed Sarbassov,
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
2004,
Pubmed Schweitz,
Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons.
1994,
Pubmed Serafini,
Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system.
1996,
Pubmed Servant,
Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
2000,
Pubmed Shim,
Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening.
2009,
Pubmed
,
Xenbase Shim,
XTRPC1-dependent chemotropic guidance of neuronal growth cones.
2005,
Pubmed
,
Xenbase Song,
cAMP-induced switching in turning direction of nerve growth cones.
1997,
Pubmed
,
Xenbase Tessier-Lavigne,
The molecular biology of axon guidance.
1996,
Pubmed Toker,
Signalling through the lipid products of phosphoinositide-3-OH kinase.
1997,
Pubmed Várnai,
Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools.
1998,
Pubmed Wang,
Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils.
2002,
Pubmed Wang,
Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones.
2005,
Pubmed
,
Xenbase Weiner,
A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.
2002,
Pubmed Wolf,
Phosphatidylinositol-3-kinase-atypical protein kinase C signaling is required for Wnt attraction and anterior-posterior axon guidance.
2008,
Pubmed Yuan,
Signalling and crosstalk of Rho GTPases in mediating axon guidance.
2003,
Pubmed
,
Xenbase Zheng,
Turning of nerve growth cones induced by neurotransmitters.
1994,
Pubmed
,
Xenbase Zheng,
Turning of nerve growth cones induced by localized increases in intracellular calcium ions.
2000,
Pubmed
,
Xenbase Zhou,
HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway.
2000,
Pubmed Zhu,
Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry.
1998,
Pubmed
