Downregulation of Transient Receptor Potential Melastatin 8 by Protein Kinase C-Mediated Dephosphorylation

Premkumar, Louis S.; Raisinghani, Manish; Pingle, Sandeep C.; Long, Cheng; Pimentel, Fátima

doi:10.1523/jneurosci.3006-05.2005

Cited by 146 publications

(167 citation statements)

References 35 publications

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“…Inversely, activation of PKC by acute application of 10 nM of PMA activated the outwardly rectifying TRPM8 current, mimicking the PSA effect (Supplementary Figure 2c). However, pretreatment of the cells with PMA over longer periods of time resulted in the inactivation of TRPM8 (Supplementary Figure 2d) due to dephosphorylation of the channel as previously described (Premkumar et al, 2005). Taken together, these results demonstrated that PSA increased TRPM8 PM activity through the B2R pathway.…”

Section: Resultssupporting

confidence: 84%

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

et al. 2010

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Although the transient receptor potential melastatin 8 (TRPM8) cold receptor is highly expressed in prostate cancer (PCa) and constitutes a promising diagnostic and prognostic indicator, the natural agonists of this channel in the prostate, as well as its physiological and pathological functions, remain unknown. In this study, we identified the well-known PCa marker, prostatespecific antigen (PSA), as a physiological TRPM8 agonist. Electrophysiological and Ca 2 þ imaging studies demonstrated that PSA activated TRPM8-mediated current by the bradykinin 2 receptor signaling pathway. Further investigation of this mechanism by cell-surface biotinylation revealed that the increase in TRPM8 current induced by PSA was due to an increase in the number of functional TRPM8 channels on the plasma membrane. Importantly, wound-healing and migration assays revealed that TRPM8 activation by PSA reduced motility of the PC3 PCa cell line, suggesting that plasma membrane TRPM8 has a protective role in PCa progression. Consequently, PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis, making this pathway a potentially important target for anticancer agent development.

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Section: Resultssupporting

confidence: 84%

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

et al. 2010

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“…TRPM8 is, however, also produced in a range of tissues that are unlikely to be regulated by temperature, including sensory neurons (41) and the malignant prostate (42). The mechanism by which TRPM8 activity is regulated in these tissues remains to be fully determined; however, several regulatory mediators have been identified, including Ca 2+ , pH, PIP2 and phosphorylation (43)(44)(45)(46)(47). In those tissues where CRISP4 and TRPM8 are coexpressed (33), our data suggests that CRISP4 is also likely to modulate TRPM8 function.…”

Section: E)mentioning

confidence: 74%

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Gibbs¹,

Orta

Reddy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

110

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The cysteine-rich secretory proteins (CRISPs) are a group of four proteins in the mouse that are expressed abundantly in the male reproductive tract, and to a lesser extent in other tissues. Analysis of reptile CRISPs and mouse CRISP2 has shown that CRISPs can regulate cellular homeostasis via ion channels. With the exception of the ability of CRISP2 to regulate ryanodine receptors, the in vivo targets of mammalian CRISPs function are unknown. In this study, we have characterized the ion channel regulatory activity of epididymal CRISP4 using electrophysiology, cell assays, and mouse models. Through patch-clamping of testicular sperm, the CRISP4 CRISP domain was shown to inhibit the transient receptor potential (TRP) ion channel TRPM8. These data were confirmed using a stably transfected CHO cell line. TRPM8 is a major cold receptor in the body, but is found in other tissues, including the testis and on the tail and head of mouse and human sperm. Functional assays using sperm from wild-type mice showed that TRPM8 activation significantly reduced the number of sperm undergoing the progesteroneinduced acrosome reaction following capacitation, and that this response was reversed by the coaddition of CRISP4. In accordance, sperm from Crisp4 null mice had a compromised ability to undergo to the progesterone-induced acrosome reaction. Collectively, these data identify CRISP4 as an endogenous regulator of TRPM8 with a role in normal sperm function.cysteine-rich secretory proteins | antigen 5 | pathogenesis-related 1 | epididymal maturation | fertility

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“…Various other mechanisms have also been proposed to underlie this phenomenon. For bradykinin (Premkumar et al, 2005), extracellular ATP (Tominaga et al, 2001), and CCL3 (N. , the involvement of protein kinase C (PKC) was also demonstrated. It was shown that NGF induces translocation of TRPV1 to the plasma membrane, thus increasing the number of active channels (X. .…”

Section: Discussionmentioning

confidence: 99%

Dual Regulation of TRPV1 by Phosphoinositides

Lukacs¹,

Thyagarajan²,

Várnai³

et al. 2007

Journal of Neuroscience

250

361

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. These data show that at low capsaicin concentrations and other moderate stimuli, PtdIns(4,5)P 2 partially inhibits TRPV1 in a cellular context, but this effect is likely to be indirect, because it is not detectable in excised patches. We conclude that phosphoinositides have both inhibitory and activating effects on TRPV1, resulting in complex and distinct regulation at various stimulation levels.

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Downregulation of Transient Receptor Potential Melastatin 8 by Protein Kinase C-Mediated Dephosphorylation

Cited by 146 publications

References 35 publications

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Dual Regulation of TRPV1 by Phosphoinositides

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