TRPV2 has a pivotal role in macrophage particle binding and phagocytosis

Link, Tiffany M; Park, Una; Vonakis, Becky M.; Raben, Daniel M.; Soloski, Mark J.; Caterina, Michael J.

doi:10.1038/ni.1842

Cited by 247 publications

(273 citation statements)

References 39 publications

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“…24,40,42 Membrane depolarization has been shown to activate the PI3K-Akt signaling in neuronal cells. 43,44 Link et al 45 have reported that TRPV2 activity induces membrane depolarization during immune complex-induced phagocytosis. We hypothesized that the influx of Na þ through Trvp5/6 under the low [Ca 2 þ ] condition may lead to membrane depolarization, which in turn increases IGF signaling in these cells.…”

Section: Discussionmentioning

confidence: 99%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2 þ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2 þ -transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2 þ ] environments. BrdU pulse-labeling experiments suggest that low [Ca 2 þ ] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2 þ ] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2 þ -selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2 þ ]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2 þ ]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2 þ ]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2 þ ]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2 þ ]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2 þ ] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2 þ deficiency.

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Section: Discussionmentioning

confidence: 99%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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“…However, recent studies suggest that TRPV2 is activated by insulin-like growth factor (Kanzaki et al, 1999). Link et al (2010) reported that TRPV2-deficient macrophages are defective in chemoattractant-elicited motility and phagocytosis. Further investigation is required to elucidate the role of TRPV2 in terms of the proliferation of HSCs stimulated by various growth factors.…”

Section: A B Cmentioning

confidence: 99%

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Park

Pang

Park

et al. 2011

Molecules and Cells

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“…TRPV2 expression has been observed in TRPV1-negative medium-to large-diameter neurons of the rat dorsal root and trigeminal ganglia and possibly in thinly myelinated nociceptors (Caterina et al, 1999;Lewinter et al, 2008). However, TRPV2 mRNA or immunoreactivity has also been detected in the brain, autonomic ganglia, spinal cord, skeletal and vascular myocytes, visceral organs (including the intestine, pancreas, spleen, and bladder), and blood cells (Caterina et al, 1999;Ichikawa and Sugimoto, 2001;Muraki et al, 2003;Kashiba et al, 2004;Lewinter et al, 2004;Inada et al, 2006;Lewinter et al, 2008;Hisanaga et al, 2009;Zanou et al, 2009;Link et al, 2010). TRPV2 expression may also be involved in the migration and proliferation of cancer cells (Caprodossi et al, 2008;Monet et al, 2010), and TRPV2-positive neurons observed in the rat myenteric plexus may be IPANs (Kashiba et al, 2004).…”

Section: Introductionmentioning

confidence: 98%

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

Mihara¹,

Boudaka²,

Shibasaki³

et al. 2010

J. Neurosci.

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Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (Ͼ52°C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca 2ϩ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.

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TRPV2 has a pivotal role in macrophage particle binding and phagocytosis

Cited by 247 publications

References 39 publications

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Identification and Functional Characterization of Ion Channels in CD34+ Hematopoietic Stem Cells from Human Peripheral Blood

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

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