ArticleThe Journal of general physiology2015
Mechanism for phosphoinositide selectivity and activation of TRPV1 ion channels.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- PI(4,5)P2-dependent and -independent roles of PI4P in the control of hormone secretion by pituitary cells.Frontiers in endocrinology · 2023Review
- Critical contributions of pre-S1 shoulder and distal TRP box in DAG-activated TRPC6 channel by PIPScientific reports · 2022Article
- Sensory TRP Channels in Three Dimensions.Annual review of biochemistry · 2022Review
- Localization of PIP5Kγ selectively in proprioceptive peripheral fields and also in sensory ganglionic satellite cells as well as neuronal cell membranes and their central terminals.Journal of anatomy · 2021Article
- Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Structural mechanisms of transient receptor potential ion channels.The Journal of general physiology · 2020Review
- The Contribution of the Ankyrin Repeat Domain of TRPV1 as a Thermal Module.Biophysical journal · 2020Article
- TRP ion channels: Proteins with conformational flexibility.Channels (Austin, Tex.) · 2019Review
- Regulation of Membrane Calcium Transport Proteins by the Surrounding Lipid Environment.Biomolecules · 2019Review
- The expanding spectrum of neurological disorders of phosphoinositide metabolism.Disease models & mechanisms · 2019Review
- Inflammatory mediators causing cutaneous chronic itch in some diseases via transient receptor potential channel subfamily V member 1 and subfamily A member 1.The Journal of dermatology · 2019Review
- Understanding phosphoinositides: rare, dynamic, and essential membrane phospholipids.The Biochemical journal · 2019Review
- Structures of TRPV2 in distinct conformations provide insight into role of the pore turret.Nature structural & molecular biology · 2019Article
- Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor.eLife · 2018Article
- Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.The Journal of general physiology · 2018Review
- TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization.Protein & cell · 2017Review
- The TrkA receptor mediates experimental thermal hyperalgesia produced by nerve growth factor: Modulation by the p75 neurotrophin receptor.Neuroscience · 2017Article
- Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice.BioMed research international · 2017Article
- Regulation of thermoTRPs by lipids.Temperature (Austin, Tex.) · 2017Review
- Exploring functional roles of TRPV1 intracellular domains with unstructured peptide-insertion screening.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although PI(4,5)P2 is believed to play an essential role in regulating the activity of numerous ion channels and transporters, the mechanisms by which it does so are unknown. Here, we used the ability of the TRPV1 ion channel to discriminate between PI(4,5)P2 and PI(4)P to localize the region of TRPV1 sequence that interacts directly with the phosphoinositide. We identified a point mutation in the proximal C-terminal region after the TRP box, R721A, that inverted the selectivity of TRPV1. Although the R721A mutation produced only a 30% increase in the EC50 for activation by PI(4,5)P2, it decreased the EC50 for activation by PI(4)P by more than two orders of magnitude. We used chemically induced and voltage-activated phosphatases to determine that PI(4)P continued to support TRPV1 activity even after depletion of PI(4,5)P2 from the plasma membrane. Our data cannot be explained by a purely electrostatic mechanism for interaction between the phosphoinositide and the protein, similar to that of the MARCKS (myristoylated alanine-rich C kinase substrate) effector domain or the EGF receptor. Rather, conversion of a PI(4,5)P2-selective channel to a PI(4)P-selective channel indicates that a structured phosphoinositide-binding site mediates the regulation of TRPV1 activity and that the amino acid at position 721 likely interacts directly with the moiety at the 5' position of the phosphoinositide.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.