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Bidaux G.,French Institute of Health and Medical Research | Bidaux G.,Lille University of Science and Technology | Bidaux G.,Institute Of Recherche Interdisciplinaire | Sgobba M.,Queens University of Belfast | And 9 more authors.
Biophysical Journal | Year: 2015

Members of the transient receptor potential (TRP) ion channel family act as polymodal cellular sensors, which aid in regulating Ca2+ homeostasis. Within the TRP family, TRPM8 is the cold receptor that forms a nonselective homotetrameric cation channel. In the absence of TRPM8 crystal structure, little is known about the relationship between structure and function. Inferences of TRPM8 structure have come from mutagenesis experiments coupled to electrophysiology, mainly regarding the fourth transmembrane helix (S4), which constitutes a moderate voltage-sensing domain, and about cold sensor and phosphatidylinositol 4,5-bisphosphate binding sites, which are both located in the C-terminus of TRPM8. In this study, we use a combination of molecular modeling and experimental techniques to examine the structure of the TRPM8 transmembrane and pore helix region including the conducting conformation of the selectivity filter. The model is consistent with a large amount of functional data and was further tested by mutagenesis. We present structural insight into the role of residues involved in intra- and intersubunit interactions and their link with the channel activity, sensitivity to icilin, menthol and cold, and impact on channel oligomerization. © 2015 Biophysical Society. Source


Laffray S.,Bordeaux University | Laffray S.,French National Center for Scientific Research | Bouali-Benazzouz R.,Bordeaux University | Bouali-Benazzouz R.,French National Center for Scientific Research | And 19 more authors.
EMBO Journal | Year: 2012

In the central nervous system, the inhibitory GABAB receptor is the archetype of heterodimeric G protein-coupled receptors (GPCRs). However, the regulation of GABAB dimerization, and more generally of GPCR oligomerization, remains largely unknown. We propose a novel mechanism for inhibition of GPCR activity through de-dimerization in pathological conditions. We show here that 14-3-3ζ, a GABAB1-binding protein, dissociates the GABAB heterodimer, resulting in the impairment of GABAB signalling in spinal neurons. In the dorsal spinal cord of neuropathic rats, 14-3-3ζ is overexpressed and weakens GABAB inhibition. Using anti-14-3-3ζ siRNA or competing peptides disrupts 14-3-3ζ/GABAB1 interaction and restores functional GABAB heterodimers in the dorsal horn. Importantly, both strategies greatly enhance the anti-nociceptive effect of intrathecal Baclofen in neuropathic rats. Taken together, our data provide the first example of endogenous regulation of a GPCR oligomeric state and demonstrate its functional impact on the pathophysiological process of neuropathic pain sensitization. © 2012 European Molecular Biology Organization. Source


Gkika D.,French Institute of Health and Medical Research | Lemonnier L.,French Institute of Health and Medical Research | Shapovalov G.,French Institute of Health and Medical Research | Gordienko D.,French Institute of Health and Medical Research | And 15 more authors.
Journal of Cell Biology | Year: 2015

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperaturesensing organs, and is regulated by downstream receptor-activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named "TRP channel-associated factors" (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. © 2015 Gkika et al. Source


Saison-Francioso O.,CNRS Institute of Electronics, Microelectronics and Nanotechnology | Leveque G.,CNRS Institute of Electronics, Microelectronics and Nanotechnology | Akjouj A.,CNRS Institute of Electronics, Microelectronics and Nanotechnology | Pennec Y.,CNRS Institute of Electronics, Microelectronics and Nanotechnology | And 3 more authors.
Journal of Physical Chemistry C | Year: 2012

In this paper, we investigate theoretically the localized plasmon resonance mode of a periodic system of bidimensional gold nanostructures coated with a dielectric layer of variable thickness. When illuminated by a plane wave in normal incidence, the interaction between the Fabry.Pérot modes established inside the layer with the particle plasmon leads to a thickness-dependent shift of the absorption maximum. Combining the Green's tensor and finite difference time domain methods, we propose first a simple description of the physical phenomenon responsible for the wavelength shift, and then analyze the effect of the background structure refractive indexes on the characteristics of the maximum wavelength evolution. © 2012 American Chemical Society. Source


Szunerits S.,Institute Of Recherche Interdisciplinaire | Coffinier Y.,Institute Of Recherche Interdisciplinaire | Galopin E.,Institute Of Recherche Interdisciplinaire | Boukherroub R.,Institute Of Recherche Interdisciplinaire
Electrochemistry Communications | Year: 2010

The paper reports on the fabrication and electrochemical investigation of boron-doped diamond nanowires (BDD NWs) electrodes. The nanowires were obtained directly from highly doped polycrystalline diamond substrates using reactive ion etching (RIE) with oxygen plasma. The technique does not require any complicated processing steps such as mask deposition or template removal. The influence of the surface state on the electrochemical characteristics is discussed. The interface with the most favourable electrochemical response is investigated for the detection of tryptophan using differential pulse voltammetry. A detection limit of 5 × 10-7 M was obtained on oxidized BDD NWs, as compared to 1 × 10-5 M recorded on planar oxidized boron-doped diamond interfaces. © 2010 Elsevier B.V. All rights reserved. Source

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