title: Transient receptor potential vanilloid 2 activation by focal mechanical stimulation requires interaction with the actin cytoskeleton and enhances growth cone motility.
abstract: We have previously reported that transient receptor potential vanilloid 2 (TRPV2) can be activated by mechanical stimulation, which enhances axonal outgrowth in developing neurons; however, the molecular mechanisms that govern the contribution of TRPV2 activation to axonal outgrowth remain unclear. In the present study, we examined this mechanism by using PC12 cells as a neuronal model. Overexpression of TRPV2 enhanced axonal outgrowth in a mechanical stimulus-dependent manner. Accumulation of TRPV2 at the cell surface was 4-fold greater in the growth cone compared with the soma. In the growth cone, TRPV2 is not static, but dynamically accumulates (within ∼100 ms) to the site of mechanical stimulation. The dynamic and acute clustering of TRPV2 can enhance very weak mechanical stimuliviafocal accumulation of TRPV2. Focal application of mechanical stimuli dramatically increased growth cone motility and caused actin reorganizationviaactivation of TRPV2. We also found that TRPV2 physically interacts with actin and that changes in the actin cytoskeleton are required for its activation. Here, we demonstrated for the first time to our knowledge that TRPV2 clustering is induced by mechanical stimulation generated by axonal outgrowth and that TRPV2 activation is triggered by actin rearrangements that result from mechanical stimulation. Moreover, TRPV2 activation enhances growth cone motility and actin accumulation to promote axonal outgrowth. Sugio, S., Nagasawa, M., Kojima, I., Ishizaki, Y., Shibasaki, K. Transient receptor potential vanilloid 2 activation by focal mechanical stimulation requires interaction with the actin cytoskeleton and enhances growth cone motility.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Shouta
authors.initials: S
authors.lastname: Sugio
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nagasawa
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan; shibasaki@gunma-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D020439:Growth Cones / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D000071446:Neuronal Outgrowth; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat
keywords: TRP channel; TRPV2; axonal outgrowth; development; neuron