A5062124982- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Pain Mechanisms and Treatments
- Axon Guidance and Neuronal Signaling
- Ocular Surface and Contact Lens
- Ion channel regulation and function
- Developmental Biology and Gene Regulation
- Neuropeptides and Animal Physiology
- Hedgehog Signaling Pathway Studies
- Retinal Development and Disorders
- Cellular Mechanics and Interactions
- Biochemical Analysis and Sensing Techniques
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Epigenetics and DNA Methylation
- interferon and immune responses
- Wnt/β-catenin signaling in development and cancer
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Circadian rhythm and melatonin
- Connexins and lens biology
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Cancer Mechanisms and Therapy
Instituto de Neurociencias
2014-2025
Consejo Superior de Investigaciones Científicas
2010-2024
Universitat de Miguel Hernández d'Elx
2000-2021
University College London
2006-2007
The vanilloid receptor-1 (TRPV1) plays a key role in the perception of peripheral thermal and inflammatory pain. TRPV1 expression channel activity are notably up-regulated by proalgesic agents. transduction pathways involved sensitization still elusive. We have used yeast two-hybrid screen to identify proteins that associate with N terminus TRPV1. report two vesicular proteins, Snapin synaptotagmin IX (Syt IX), strongly interact vitro vivo N-terminal domain. In primary dorsal root ganglion...
Vanilloid receptor subunit 1 (VR1) is a nonselective cation channel that integrates multiple pain-producing stimuli. VR1 channels are blocked with high efficacy by the well established noncompetitive antagonist ruthenium red and exhibit permeability to divalent cations. The molecular determinants define these functional properties remain elusive. We have addressed this question evaluated site-specific neutralization contribution on pore of acidic residues located in putative region. Mutant...
Transient receptor potential channels are a family of cation involved in diverse cellular functions. Most these expressed the nervous system and play key role sensory physiology. TRPM8 (transient melastatine 8), member this family, is activated by cold, cooling substances such menthol icilin voltage. Although thermosensitive channel highly cold neurons, mechanisms underlying its temperature sensitivity still poorly understood. Here we show that, localized cholesterol-rich specialized...
Activity-dependent changes in neurons of the rat superficial dorsal horn are crucial for induction and maintenance neuropathic inflammatory pain states. To identify molecular mechanisms underlying this sensitization neurons, we undertook a genome-wide microarray profiling gene transcripts at various times after peripheral inflammation ankle joint. At early time points, upregulation expression dominated, but by 7 d, downregulation was predominant. Two to 24 h inflammation, identified small...
Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate very wide range from innocuous to noxious. The molecular mechanism responsible for variable sensitivity individual temperature is unclear. To address this question, we performed detailed channel expression analysis cold-sensitive neurons, combining bacterial artificial chromosome (BAC) transgenesis with...
Abstract The cold‐ and menthol‐activated ion channel transient receptor potential subfamily M member 8 (TRPM8) is the principal detector of environmental cold in mammalian sensory nerve endings. Although it mainly expressed a subpopulation peripheral neurons, has also been identified non‐neuronal tissues. Here, we show, by situ hybridization (ISH) analysis transgenic reporter expression two different mouse strains, that TRPM8 central nervous system. present at much lower levels than found...
TRPM8 is a member of the transient receptor potential ion channel superfamily, which expressed in sensory neurons and activated by cold cooling compounds, such as menthol. Activation agonists takes place through shifts its voltage activation curve, allowing opening at physiological membrane potentials. Here, we studied role N-glycosylation occurring pore loop on function channel. Using heterologous expression recombinant channels HEK293 cells found that unglycosylated mutant (N934Q) displays...
Abstract Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline perception. Here, we analyze changes occurring with in trigeminal ganglion (TG), TRPM8‐expressing cold thermoreceptor innervating mouse cornea, which participate regulation basal tearing blinking have been implicated pathogenesis dry eye disease (DED). TG cell bodies axonal branches were examined line (TRPM8 BAC ‐EYFP) expressing fluorescent reporter. In 3 months...
The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship lost when tumorigenic stimuli induce uncontrolled cell proliferation, generating tumours such us neurofibromas and schwannomas. also re-enter the cycle following nerve injury during process Wallerian degeneration. In both cases proliferation finally arrested. We show that neurofibroma, induction Jmjd3 (jumonji domain containing 3, histone lysine demethylase) removes trimethyl groups on lysine-27...
The Wnt pathway is involved in a wide array of biological processes during development and deregulated many pathological scenarios. In neurons, proteins promote both axon extension repulsion, but the molecular mechanisms underlying these opposing axonal responses are unknown. Here, we show that Wnt5a expressed at optic chiasm midline promotes crossing retinal axons by triggering an alternative depends on accumulation βcatenin does not activate canonical pathway. ipsilateral transcription...
A characteristic feature of many vertebrate axons is their wrapping by a lamellar stack glially derived membranes known as the myelin sheath. Myelin cholesterol-rich membrane that allows for rapid saltatory nerve impulse conduction. Axonal neuregulins instruct glial cells on when and how much they should produce. However, neuregulin regulates sheath development thickness unknown. Here we show receptors are activated drops in plasma cholesterol, suggesting can sense sterol levels. In Schwann...
Abstract Aim Physiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central peripheral clocks participate this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role function. Methods We used reporter mouse lines TRPM8‐deficient mice. mRNA levels were determined situ hybridization or RT‐qPCR protein immunofluorescence. A telemetry system was to measure core body temperature (Tc). Results...
Abstract The stimulus-regulated transcription factor Serum Response Factor (SRF) plays an important role in diverse neurodevelopmental processes related to structural plasticity and motile functions, although its precise mechanism of action has not yet been established. To further define the SRF neural development distinguish between cell-autonomous non effects, we bidirectionally manipulated activity through gene transduction assays that allow visualization individual neurons their...
Abstract Actin cytoskeleton dynamics is critical for nervous system development and function, yet the role of alternative splicing in controlling these processes poorly understood. A highly conserved subset neuronal-specific microexons coordinates fundamental aspects biology. exons enriched genes involved actin cytoskeleton, their functions are unknown. Here, we focus on a microexon DAAM1, member formin-homology-2 (FH2) domain class proteins, which have diverse associated with reorganization...