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 stimuli focal accumulation of TRPV2. Focal application of mechanical stimuli dramatically increased growth cone motility and caused actin reorganization activation 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.

Retinal Detachment-Induced Müller Glial Cell Swelling Activates TRPV4 Ion Channels and Triggers Photoreceptor Death at Body Temperature

“…8 ). This finding is consistent with our other previous studies showing the involvement of TRP-channel mechanosensor functions in a variety of physiological functions, including the following: (1) TRPV2-dependent sensation of membrane stretch by developing neurons, which enhances axon outgrowth ( Shibasaki et al, 2010 ; Sugio et al, 2017 ); (2) TRPV2 mechanosensitivity that regulates intestinal motility ( Regillo and Bensen, 1988 ); (3) body temperature- and movement-dependent activation of choroid plexus epithelial cells that further activates TRPV4 through epoxyeicosatrienoic acid production ( Takayama et al, 2014 ); and (4) TRPV4-dependent sensation of urinary bladder distension, which can be converted to ATP signals in the micturition reflex pathway ( Mochizuki et al, 2009 ; Shibasaki, 2016 ). The mechanisms by which TRPV4 contributes to Müller glial MCP-1 release remain to be clarified.…”

Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2

“…TRPV2 is activated by mechanical stimuli [ 14 , 15 ], temperatures above 52 °C [ 16 ] or by chemicals such as 2-Aminoethyl diphenylborinate and cannabidiol [ 17 , 18 ]. Controversial results concerning activation and function are reported and may be due to species-related differences [ 19 ].…”

Identification of two natural coumarin enantiomers for selective inhibition of TRPV2 channels

“…We obtained racemic B304 was as a white amorphous powder. Its molecular formula was deduced as C 17 H 20 O 5 from the 13 The NMR data indicate that B304 is murraxocin, 45 but its specific rotation approached zero and no Cotton effects observed ( Figures S3 and S4), suggesting that B304 is a pair of enantiomers coexisted as a racemic mixture. Separation of B304 by chiral-phase HPLC gave rise to a pair of enantiomers B304-1 and B304-2 in an approximate ratio of 1:1 ( Figure 1A-C Figure 1D).…”

“…4,5 TRPV2 is widely expressed in tissues including adipose tissue, and involved in a variety of physiological processes and functions. [9][10][11][12][13] Brown adipose tissue (BAT) is metabolically active in adult humans, 14,15 and primarily functions as a source of energy for thermoregulation. 16 Brown adipocytes are first differentiated from mesenchymal stem cells to brown pre-adipocytes before full development into brown adipocytes.…”