A5040666828- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Ion Channels and Receptors
- Genetics, Aging, and Longevity in Model Organisms
- Lipid Membrane Structure and Behavior
- Cardiac electrophysiology and arrhythmias
- Circadian rhythm and melatonin
- Mass Spectrometry Techniques and Applications
- Genetic Syndromes and Imprinting
- Electron Spin Resonance Studies
- Neuroscience and Neuropharmacology Research
- Thermoregulation and physiological responses
- Neurogenetic and Muscular Disorders Research
- Alcohol Consumption and Health Effects
- Spaceflight effects on biology
- Biochemical effects in animals
- Chemical and Physical Studies
- Adipose Tissue and Metabolism
- Blood properties and coagulation
- Biochemical Analysis and Sensing Techniques
- Growth Hormone and Insulin-like Growth Factors
- Plant Disease Resistance and Genetics
- Neurobiology and Insect Physiology Research
- Dietary Effects on Health
- Phytochemicals and Antioxidant Activities
Tecnológico de Monterrey
2025
Texas Tech University
2025
Texas Tech University Health Sciences Center
2025
University of Tennessee Health Science Center
2014-2024
The University of Texas Health Science Center at Houston
2024
Stanford University
2009-2018
Pontificia Universidad Católica de Valparaíso
2013
University of Chicago
2006-2009
University of Virginia
2006-2008
Howard Hughes Medical Institute
2008
Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture remodeling, cell migration, erythrocyte volume. identity of the components that modulate function remain largely unknown. Using lipid profiling analyses, we here identify dietary fatty acids tune mechanical response. We find margaric acid, a...
TRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection cerebrospinal fluid flow. However, many instances it is unclear whether primary transducers mechanical force these processes. In this study, we tested stretch activation eleven from six mammalian subfamilies. We found that were insensitive to short membrane stretches cellular...
KcsA is a proton-activated, voltage-modulated K + channel that has served as the archetype pore domain in Kv superfamily. Here, we have used synthetic antigen-binding fragments (Fabs) crystallographic chaperones to determine structure of full-length at 3.8 Å, well its isolated C-terminal 2.6 Å. The KcsA–Fab complex reveals well-defined, 4-helix bundle projects ≈70 Å toward cytoplasm. This promotes ≈15° bending inner gate, tightening diameter and shifting narrowest point 2 turns helix below....
The mechanosensitive channel of small conductance (MscS) is a key determinant in the prokaryotic response to osmotic challenges. We determined structural rearrangements associated with MscS activation membranes, using functorial measurements, electron paramagnetic resonance spectroscopy, and computational analyses. was trapped its open conformation after transbilayer pressure profile modified through asymmetric incorporation lysophospholipids. transition from closed state accompanied by...
Mechanoelectrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT membrane phospholipids, part because few techniques available altering plasma composition vivo. Here, we leverage genetic dissection, chemical complementation, optogenetics to establish that arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, enhances sensation mechanoelectrical activity while...
Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation TRPV4 channel has been implicated endothelium-dependent vasorelaxation. Here, we studied contribution PUFAs function by precisely manipulating acid content Caenorhabditis elegans. By genetically depriving worms PUFAs, determined that metabolism required for activity. Functional, lipid metabolome, and...
Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations in muscle- and joint-related genes, the anatomical defects originate cell-autonomously within musculoskeletal system. However, gain-of-function PIEZO2, principal mechanosensor somatosensation, cause subtype 5 (DA5) through unknown mechanisms. We show expression PIEZO2 mutation proprioceptive sensory neurons mainly innervate muscle spindles tendons sufficient...
Abstract Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression the E3 ubiquitin-protein ligase UBE3A maternal allele in neurons. Individuals with display impaired coordination, poor balance, gait ataxia. PIEZO2 mechanosensitive ion channel essential for coordination balance. Here, we report that activity reduced Ube3a deficient male female mouse sensory neurons, human Merkel cell carcinoma line...
Abstract PIEZO2 is the essential transduction channel for touch discrimination, vibration, and proprioception. Mice humans lacking Piezo2 experience severe mechanosensory proprioceptive deficits fail to develop tactile allodynia. Bradykinin, a proalgesic agent released during inflammation, potentiates activity. Molecules that decrease function could reduce heightened responses inflammation. Here, we find dietary fatty acid margaric (MA) decreases in dose-dependent manner. Chimera analyses...
Intestinal epithelial tight junction disruption is a primary contributing factor in alcohol-associated endotoxemia, systemic inflammation, and multiple organ damage. Ethanol acetaldehyde disrupt junctions by elevating intracellular Ca2+. Here we identify TRPV6, Ca2+-permeable channel, as responsible for alcohol-induced elevation of Ca2+, intestinal barrier dysfunction, inflammation. elicit TRPV6 ionic currents Caco-2 cells. Studies cell monolayers mouse organoids show that deficiency or...
Significance The TRPV1 channel integrates noxious stimuli from multiple sources to evoke an appropriate pain response. However, while different distinct activation, the underlying molecular mechanisms remain unclear. Here, we aim at elucidating structural determinants that regulate responses two toxins: capsaicin and double-knot toxin (DkTx). We found pore turret domain imposes opposite effects on these toxins. While it restricts ion conductance of DkTx-evoked current, stabilizes open state...
This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established emerging mechanosensitive (MS) proteins, their distribution across protein families phyla, current future challenges in the study these important proteins partners. MS are essential for tissue development, cellular motion, osmotic homeostasis, sensing external self-generated mechanical cues like those responsible touch proprioception. Though...
Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized sickle erythrocytes that are prone to hemolysis, causing anemia and vaso-occlusion crises. In erythrocytes, hemoglobin aggregation followed altered cation permeability subsequent dehydration. Interventions restore can decrease hemolysis ameliorate symptoms associated with SCD. PIEZO1 non-selective mechanosensitive channel regulates erythrocyte volume. Gain-of-function (GOF)...
The efficacy of orally administered trimethoprim-sulfamethoxazole was compared with that oral amoxicillin in therapy typhoid fever due to both epidemic chloramphenicol-resistant and endemic chloramphenicol-sensitive Salmonella typhi. Both drug regimens were effective comparable value treatment infections, as measured by duration (124 hr 115 hr, respectively) bacteremia (1.0 0.4 days, respectively). Trimethoprim-sulfamethoxazole infections S. typhi resulted more rapid lysis than did therapy....
Abstract This paper reports the expression and localization of linamarase in roots two cassava (Manihot esculentaCrantz) cultivars low high cyanide. Two different patterns activity were observed. In low-cyanide type, young leaves displayed very enzyme during early plant growing stage (3 months), whereas root peel, increased progressively to reach a peak 11-month-old plants. Conversely, high-cyanide cultivar (HCV), peel decreased growth cycle, expanded peaked The accumulation linamarin showed...
PIEZO channels are force sensors essential for physiological processes, including baroreception and proprioception. The Caenorhabditis elegans genome encodes an orthologue gene of the Piezo family, pezo-1, which is expressed in several tissues, pharynx. This myogenic pump component C. alimentary canal, whose contraction relaxation modulated by mechanical stimulation elicited food content. Whether pezo-1 a mechanosensitive ion channel contributes to pharyngeal function remains unknown. Here,...
The sense of touch is crucial for cognitive, emotional, and social development relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization these channels, physiological factors control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, various mouse strains (males females analyzed separately) to investigate role calmodulin-like Ca 2+ sensor,...
The mechanosensitive channel of small conductance (MscS) plays a critical role in the osmoregulation prokaryotic cells. crystal structure MscS revealed homoheptamer with three transmembrane segments and large cytoplasmic domain. It has been suggested that depicts an open state, but its actual functional conformation remains controversial. In pursuit spectroscopical approaches to gating, we determined standard purification methods yield two forms MscS, considerable amount unfolded channel....