Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00510413" target="_blank" >RIV/67985823:_____/19:00510413 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10396661

Výsledek na webu

<a href="https://doi.org/10.1111/febs.14931" target="_blank" >https://doi.org/10.1111/febs.14931</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.14931" target="_blank" >10.1111/febs.14931</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials

Popis výsledku v původním jazyce

The transient receptor potential ankyrin 1 (TRPA1) channel is a polymodal sensor of environmental irritant compounds, endogenous proalgesic agents, and cold. Upon activation, TRPA1 channels increase cellular calcium levels via direct permeation and trigger signaling pathways that hydrolyze phosphatidylinositol-4,5-bisphosphate (PIP2) in the inner membrane leaflet. Our objective was to determine the extent to which a putative PIP2-interaction site (Y1006-Q1031) is involved in TRPA1 regulation. The interactions of two specific peptides (L992-N1008 and T1003-P1034) with model lipid membranes were characterized by biophysical approaches to obtain information about affinity, peptide secondary structure, and peptide effect in the lipid organization. The results indicate that the two peptides interact with lipid membranes only if PIP2 is present and their affinities depend on the presence of calcium. Using whole-cell electrophysiology, we demonstrate that mutation at F1020 produced channels with faster activation kinetics and with a rightward shifted voltage-dependent activation curve by altering the allosteric constant that couples voltage sensing to pore opening. We assert that the presence of PIP2 is essential for the interaction of the two peptide sequences with the lipid membrane. The putative phosphoinositide-interacting domain comprising the highly conserved F1020 contributes to the stabilization of the TRPA1 channel gate.

Název v anglickém jazyce

Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials

Popis výsledku anglicky

The transient receptor potential ankyrin 1 (TRPA1) channel is a polymodal sensor of environmental irritant compounds, endogenous proalgesic agents, and cold. Upon activation, TRPA1 channels increase cellular calcium levels via direct permeation and trigger signaling pathways that hydrolyze phosphatidylinositol-4,5-bisphosphate (PIP2) in the inner membrane leaflet. Our objective was to determine the extent to which a putative PIP2-interaction site (Y1006-Q1031) is involved in TRPA1 regulation. The interactions of two specific peptides (L992-N1008 and T1003-P1034) with model lipid membranes were characterized by biophysical approaches to obtain information about affinity, peptide secondary structure, and peptide effect in the lipid organization. The results indicate that the two peptides interact with lipid membranes only if PIP2 is present and their affinities depend on the presence of calcium. Using whole-cell electrophysiology, we demonstrate that mutation at F1020 produced channels with faster activation kinetics and with a rightward shifted voltage-dependent activation curve by altering the allosteric constant that couples voltage sensing to pore opening. We assert that the presence of PIP2 is essential for the interaction of the two peptide sequences with the lipid membrane. The putative phosphoinositide-interacting domain comprising the highly conserved F1020 contributes to the stabilization of the TRPA1 channel gate.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA19-03777S" target="_blank" >GA19-03777S: Molekulární mechanizmy regulace teplotně citlivých TRP iontových kanálů v nociceptivních neuronech</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

FEBS Journal

ISSN

1742-464X

e-ISSN

—

Svazek periodika

286

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

20

Strana od-do

3664-3683

Kód UT WoS článku

000486201000010

EID výsledku v databázi Scopus

2-s2.0-85067398939