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J Neurosci
2013 Jan 02;331:273-85. doi: 10.1523/JNEUROSCI.2142-12.2013.
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Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth.
Kerstein PC, Jacques-Fricke BT, Rengifo J, Mogen BJ, Williams JC, Gottlieb PA, Sachs F, Gomez TM.
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Intracellular Ca(2+) signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca(2+) transients. Ca(2+) influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca(2+) influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.
Alderton,
Calcium influx through calcium leak channels is responsible for the elevated levels of calcium-dependent proteolysis in dystrophic myotubes.
2000, Pubmed
Alderton,
Calcium influx through calcium leak channels is responsible for the elevated levels of calcium-dependent proteolysis in dystrophic myotubes.
2000,
Pubmed Calderwood,
The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation.
1999,
Pubmed Dent,
GAP-43 phosphorylation is dynamically regulated in individual growth cones.
1992,
Pubmed Discher,
Tissue cells feel and respond to the stiffness of their substrate.
2005,
Pubmed Doyle,
Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes.
2004,
Pubmed Engler,
Matrix elasticity directs stem cell lineage specification.
2006,
Pubmed Franco,
Calpain-mediated proteolysis of talin regulates adhesion dynamics.
2004,
Pubmed Frey,
Cellular responses to substrate topography: role of myosin II and focal adhesion kinase.
2006,
Pubmed Glading,
Cutting to the chase: calpain proteases in cell motility.
2002,
Pubmed Gomez,
Filopodial calcium transients promote substrate-dependent growth cone turning.
2001,
Pubmed
,
Xenbase Gomez,
The molecular basis for calcium-dependent axon pathfinding.
2006,
Pubmed Gómez,
Working with Xenopus spinal neurons in live cell culture.
2003,
Pubmed
,
Xenbase Gottlieb,
Neurite outgrowth from PC12 cells is enhanced by an inhibitor of mechanical channels.
2010,
Pubmed
,
Xenbase Grynkiewicz,
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
1985,
Pubmed Henley,
Guiding neuronal growth cones using Ca2+ signals.
2004,
Pubmed Hong,
Calcium signalling in the guidance of nerve growth by netrin-1.
2000,
Pubmed
,
Xenbase Jacques-Fricke,
Ca2+ influx through mechanosensitive channels inhibits neurite outgrowth in opposition to other influx pathways and release from intracellular stores.
2006,
Pubmed
,
Xenbase Kostic,
RPTPalpha is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons.
2007,
Pubmed Kroese,
Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics.
1989,
Pubmed Lee,
Regulation of cell movement is mediated by stretch-activated calcium channels.
1999,
Pubmed Letourneau,
Distribution and possible interactions of actin-associated proteins and cell adhesion molecules of nerve growth cones.
1989,
Pubmed Li,
Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor.
2005,
Pubmed
,
Xenbase Liedtke,
Abnormal osmotic regulation in trpv4-/- mice.
2003,
Pubmed Lo,
Cell movement is guided by the rigidity of the substrate.
2000,
Pubmed Loukin,
Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force.
2010,
Pubmed
,
Xenbase Maroto,
TRPC1 forms the stretch-activated cation channel in vertebrate cells.
2005,
Pubmed
,
Xenbase Matthews,
Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins.
2010,
Pubmed Moon,
Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo.
2010,
Pubmed
,
Xenbase Moore,
Stretchy proteins on stretchy substrates: the important elements of integrin-mediated rigidity sensing.
2010,
Pubmed Moore,
Traction on immobilized netrin-1 is sufficient to reorient axons.
2009,
Pubmed Moore,
Netrin-1 attracts axons through FAK-dependent mechanotransduction.
2012,
Pubmed Munevar,
Regulation of mechanical interactions between fibroblasts and the substratum by stretch-activated Ca2+ entry.
2004,
Pubmed Myers,
Regulation of axonal outgrowth and pathfinding by integrin-ECM interactions.
2011,
Pubmed Myers,
Focal adhesion kinase promotes integrin adhesion dynamics necessary for chemotropic turning of nerve growth cones.
2011,
Pubmed
,
Xenbase Nguyen,
Pre-existing pathways promote precise projection patterns.
2002,
Pubmed Nishiyama,
Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning.
2003,
Pubmed
,
Xenbase Oda,
pp60src is an endogenous substrate for calpain in human blood platelets.
1993,
Pubmed Ostrow,
cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels.
2003,
Pubmed Pelham,
Cell locomotion and focal adhesions are regulated by substrate flexibility.
1997,
Pubmed Rajnicek,
Guidance of CNS growth cones by substratum grooves and ridges: effects of inhibitors of the cytoskeleton, calcium channels and signal transduction pathways.
1997,
Pubmed
,
Xenbase Renaudin,
Organization of point contacts in neuronal growth cones.
1999,
Pubmed Robles,
Filopodial calcium transients regulate growth cone motility and guidance through local activation of calpain.
2003,
Pubmed
,
Xenbase Robles,
Src-dependent tyrosine phosphorylation at the tips of growth cone filopodia promotes extension.
2005,
Pubmed
,
Xenbase Robles,
Focal adhesion kinase signaling at sites of integrin-mediated adhesion controls axon pathfinding.
2006,
Pubmed
,
Xenbase Shim,
XTRPC1-dependent chemotropic guidance of neuronal growth cones.
2005,
Pubmed
,
Xenbase Spagnoli,
Atomic force microscopy analysis of cell volume regulation.
2008,
Pubmed Strotmann,
OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.
2000,
Pubmed Strübing,
Formation of novel TRPC channels by complex subunit interactions in embryonic brain.
2003,
Pubmed Suchyna,
Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers.
2004,
Pubmed Takei,
Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones.
1998,
Pubmed Tian,
Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels.
2010,
Pubmed Vriens,
Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4.
2004,
Pubmed Wang,
Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones.
2005,
Pubmed
,
Xenbase Wei,
Calcium flickers steer cell migration.
2009,
Pubmed Wen,
BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.
2007,
Pubmed
,
Xenbase Wen,
A CaMKII/calcineurin switch controls the direction of Ca(2+)-dependent growth cone guidance.
2004,
Pubmed
,
Xenbase Willits,
Effect of collagen gel stiffness on neurite extension.
2004,
Pubmed Woo,
Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion.
2009,
Pubmed
,
Xenbase Wozniak,
Mechanotransduction in development: a growing role for contractility.
2009,
Pubmed Wu,
Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses.
1999,
Pubmed Wu,
International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family.
2010,
Pubmed Xu,
Generation of functional ion-channel tools by E3 targeting.
2005,
Pubmed Yang,
Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions.
1989,
Pubmed
,
Xenbase Zhang,
A tension-induced mechanotransduction pathway promotes epithelial morphogenesis.
2011,
Pubmed
