Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurosci
2013 Jan 02;331:273-85. doi: 10.1523/JNEUROSCI.2142-12.2013.
Show Gene links
Show Anatomy links
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
.
???displayArticle.abstract???
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
