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| http://dx.doi.org/10.1085/jgp.200810138 | DOI Listing |
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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 PDFThe sperm-specific K channel Slo3 is inhibited by albumin and steroids contained in reproductive fluids.
Front Cell Dev Biol
August 2024
Centre of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany.
To locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca channel CatSper has come into focus as a polymodal sensor used by human sperm to register ligands released into the female genital tract.
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 journey from molecule to physiology and tools for drug discovery targeting the transient receptor potential vanilloid type 1 (TRPV1) channel.
Front Pharmacol
January 2024
Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
The heat and capsaicin receptor TRPV1 channel is widely expressed in nerve terminals of dorsal root ganglia (DRGs) and trigeminal ganglia innervating the body and face, respectively, as well as in other tissues and organs including central nervous system. The TRPV1 channel is a versatile receptor that detects harmful heat, pain, and various internal and external ligands. Hence, it operates as a polymodal sensory channel.
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