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Forty sites of TRP channel regulation.
Curr Opin Chem Biol
November 2024
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Electronic address:
Transient receptor potential (TRP) channels are polymodal molecular sensors that integrate chemical, thermal, mechanical and electrical stimuli and convert them into ionic currents that regulate senses of taste, smell, vision, hearing, touch and contribute to perception of temperature and pain. TRP channels are implicated in the pathogenesis of numerous human diseases, including cancers, and represent one of the most ardently pursued drug targets. Recent advances in structural biology, particularly associated with the cryo-EM "resolution revolution", yielded numerous TRP channel structures in complex with ligands that might have therapeutic potential.
View Article and Find Full Text PDFTubulin interaction at tubulin-binding sequence 1 (TBS1) is required for proper surface expression and TRPV1 channel activity.
Life Sci
November 2024
School of Biological Sciences, National Institute of Science Education and Research, HBNI, Khordha, Jatni, Odisha 752050, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India. Electronic address:
TRPV1, a polymodal and nonselective cation channel has unique gating mechanisms which is regulated by supramolecular complexes at the plasma membrane formed with membrane proteins, lipids and kinase pathways. Crosstalk between microtubule cytoskeleton with TRPV1 at various level has been established. Previously we demonstrated that the positively-charged residues present at specific tubulin-binding stretch sequences (i.
View Article and Find Full Text PDFCapsaicin-insensitivity of TRPV1-R575D mutant located at the lipid-water-interface region can be rescued by either extracellular Ca-chelation or cholesterol reduction.
Neurochem Int
October 2024
School of Biological Sciences, National Institute of Science Education and Research, HBNI, Khordha, Jatni, Odisha, 752050, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400094, India. Electronic address:
Article Synopsis
- TRPV1 is a unique ion channel with distinct structural properties, and the mutant TRPV1-R575D shows reduced interaction with membrane cholesterol, leading to "ligand-insensitivity" and high cellular lethality under control conditions.
- The lethality from TRPV1-R575D can be mitigated by using a specific inhibitor (5'I-RTX) or by introducing a second mutation (D576R) near R575D.
- The study reveals that conditions like lowering extracellular Ca or depleting membrane cholesterol can rescue the "ligand-insensitivity" of TRPV1-R575D and highlights the importance of intracellular calcium for channel gating in both the wild type and mutant forms.
A hydrophobic funnel governs monovalent cation selectivity in the ion channel TRPM5.
Biophys J
October 2024
Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom. Electronic address:
A key capability of ion channels is the facilitation of selective permeation of certain ionic species across cellular membranes at high rates. Due to their physiological significance, ion channels are of great pharmaceutical interest as drug targets. The polymodal signal-detecting transient receptor potential (TRP) superfamily of ion channels forms a particularly promising group of drug targets.
View Article and Find Full Text PDFThe Feel of Speech: Multisystem and Polymodal Somatosensation in Speech Production.
J Speech Lang Hear Res
May 2024
Purpose: The oral structures such as the tongue and lips have remarkable somatosensory capacities, but understanding the roles of somatosensation in speech production requires a more comprehensive knowledge of somatosensation in the speech production system in its entirety, including the respiratory, laryngeal, and supralaryngeal subsystems. This review was conducted to summarize the system-wide somatosensory information available for speech production.
Method: The search was conducted with PubMed/Medline and Google Scholar for articles published until November 2023.
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