A5035304780- Ion Channels and Receptors
- Cellular transport and secretion
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Receptor Mechanisms and Signaling
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Calcium signaling and nucleotide metabolism
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- Bacterial Genetics and Biotechnology
- Media, Journalism, and Communication History
- Hormonal Regulation and Hypertension
- Toxin Mechanisms and Immunotoxins
- Advanced Fluorescence Microscopy Techniques
- Cardiac electrophysiology and arrhythmias
- Ion Transport and Channel Regulation
- Signaling Pathways in Disease
- Hippo pathway signaling and YAP/TAZ
- Neurogenesis and neuroplasticity mechanisms
University of Pittsburgh
2018-2025
Universidad Nacional Autónoma de México
2012-2020
Instituto Nacional de Cardiología
2014-2017
A signaling complex enables the compartmentalized regulation of cyclic AMP by calcium entering through a specific channel.
Class I phosphoinositide 3-OH kinase (PI3K) signaling is central to animal growth and metabolism, pathological disruption of this pathway affects cancer diabetes. However, the specific spatial/temporal dynamics roles its minor lipid messenger, phosphatidylinositol (3,4)-bisphosphate (PI(3,4)P2), are not well understood. This owes principally a lack tools study scarce lipid. Here we developed high-sensitivity genetically encoded biosensor for PI(3,4)P2, demonstrating high selectivity...
The lipid molecule phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] controls all aspects of plasma membrane (PM) function in animal cells, from its selective permeability to the attachment cytoskeleton. Although disruption PI(4,5)P2 is associated with a wide range diseases, it remains unclear how cells sense and maintain levels support various cell functions. Here, we show that PIP4K family enzymes, which synthesize via minor pathway, also as sensors tonic levels. PIP4Ks are recruited PM...
Abstract STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). is sensor, which oligomerizes activates Orai channels when levels drop inside endoplasmic reticulum (ER). The series molecular rearrangements that undergoes until final activation require direct exposure domain SOAR (Stim Activating Region). In addition to these complex rearrangements, other constituents like lipids at plasma membrane, play critical...
The lipid phosphatidyl-D-myo-inositol-4,5-bisphosphate [PI(4,5)P2] is a master regulator of plasma membrane (PM) function. Its effector proteins regulate transport, signaling, and cytoskeletal processes that define PM structure How single type regulates so many parallel unclear. We tested the hypothesis spatially separate PI(4,5)P2 pools associate with different complexes. mobility was measured using biosensors by single-particle tracking. found lipids including diffuse rapidly (∼0.3 µm2/s)...
Squamous cell carcinoma of the head and neck (SCCHN) is a devastating disease that continues to have low cure rates despite recent advances in therapies. Cisplatin most used chemotherapy agent, treatment failure largely driven by resistance this drug. Amplification chromosomal band 11q13 occurs ∼30% SCCHN tumors. This region harbors ANO1 gene encodes TMEM16A ion channel, which responsible for calcium-activated chloride transport epithelial tissues. overexpression associated with cisplatin...
The mechanism determining the preferential stimulation of one heterotrimeric G protein signaling pathway over another by a ligand remains undetermined. By reporting cryogenic electron microscopy (cryo-EM) structure parathyroid hormone (PTH) type 1 receptor (PTH1R) complexed with Gq and comparing its allosteric dynamics that PTH1R in complex s , we uncover underlying such preferences. We show an coupling between PTH C-terminal helix α5 Gα subunit controls stability specific protein, or q ....
The central and pervasive influence of cAMP on cellular functions underscores the value stringent control organization adenylyl cyclases (ACs) in plasma membrane. Biochemical data suggest that ACs reside membrane rafts could compartmentalize intermediary scaffolding proteins associated regulatory elements. However, little is known about or regulation dynamic behaviour a context. present study examines these issues, using confocal image analysis various AC8 constructs, combined with...
Abstract Store-operated calcium entry (SOCE) is an essential influx mechanism in animal cells. One of the most important auto regulatory control systems involves calcium-dependent inactivation (CDI) Orai channel, which prevents excessive influx. In present study we analyze role two channels induction CDI on Orai1. Here show that entering through freely diffusing TRPV1 induce strong Orai1 while P2X 4 channel does not. can because both were found close proximity cell membrane. This was not...
Abstract N-methyl-D-aspartate receptors (NMDAR) are glutamate-gated calcium channels named after their artificial agonist. NMDAR implicated in cell proliferation under normal and pathophysiological conditions. However, the role of during mitosis has not yet been explored individual cells. We found that neurotransmitter-evoked entry via endogenous cortical astrocytes was transient mitosis. The same occurred HEK293 cells transfected with NR1/NR2A subunits NMDAR. This due to phosphorylation...
Abstract The lipid molecule phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P 2 ) controls all aspects of plasma membrane (PM) function in animal cells, from its selective permeability to the attachment cytoskeleton. Although disruption PI(4,5)P is associated with a wide range diseases, it remains unclear how cells sense and maintain levels support various cell functions. Here, we show that PIP4K family enzymes synthesize via minor pathway, also as sensors tonic levels. PIP4Ks are recruited...
Orai and STIM are the basic components of a highly complex regulated mechanism for Ca 2+ entry into cell, known as store-operated calcium (SOCE). The activation plasma membrane G-protein-coupled receptors associated with phospholipase C cascade results in rapid massive production inositol 1,4,5-triphosphate (IP 3 ). This second messenger triggers efflux from endoplasmic reticulum cytosol, resulting oligomerization stromal interacting molecule (STIM1), sensor ER . STIM1 oligomers (the...
<b>Abstract ID 81135</b> <b>Poster Board 570</b> This study addresses a fundamental question in G protein-coupled receptor (GPCR) signaling by determining how peptide ligand, its receptor, and b-arrestin (barr) assemble ternary cell membrane complex. Here, fluorescent moieties were attached to the parathormone (PTH) (PTH<sub>1</sub>R) as prototypical GPCR, PTH, barr clathrin. By recording dual-color single-molecule imaging at plasma of live cells, we found that PTH<sub>1</sub>R exhibits...
Abstract The assembly of a peptide ligand, its receptor, and β-arrestin (βarr) into ternary complex within the cell membrane is crucial aspect G protein-coupled receptor (GPCR) signaling. We explore this by attaching fluorescent moieties to parathyroid hormone (PTH) type 1 (PTH R), using PTH as prototypical hormone, along with βarr clathrin, recording dual-color single-molecule imaging at plasma live cells. Here we show that R exhibits near-Brownian diffusion, whereas unbound displays...