Sensitization of
            glutamate receptor
            ‐mediated pain behaviour via nerve growth factor‐dependent phosphorylation of transient receptor potential V1 under inflammatory conditions

Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca2+-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca2+-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca2+signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca2+signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function.

Download Full-text

Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

AJP Cell Physiology ◽

10.1152/ajpcell.00614.2008 ◽

2009 ◽

Vol 297 (2) ◽

pp. C360-C368 ◽

Cited By ~ 85

Author(s):

Elie Abed ◽

Robert Moreau

Keyword(s):

Growth Factor ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Platelet Derived Growth Factor ◽

Human Osteoblast ◽

Osteoblast Proliferation ◽

Transient Receptor ◽

And Migration ◽

Stimulation Of ◽

Proliferation And Migration

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg2+) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg2+ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg2+ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg2+, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg2+ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg2+ influx, proliferation, and migration. Our results indicate that extracellular Mg2+ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg2+ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

Download Full-text