Clustering of the zeta-Chain Can Initiate T Cell Receptor Signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F20%3A10426295" target="_blank" >RIV/00216208:11310/20:10426295 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xJYlJevQa6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xJYlJevQa6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21103498" target="_blank" >10.3390/ijms21103498</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Clustering of the zeta-Chain Can Initiate T Cell Receptor Signaling

Popis výsledku v původním jazyce

T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of zeta -chain in a light controlled manner. We showed that spatial clustering of the zeta -chain intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of zeta -chain, Zap70, PLC gamma, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate zeta -chain phosphorylation upon zeta -chain clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed zeta -chain clusters at the plasma membrane. Taken together, our data demonstrated the biophysical relevance of receptor clustering in TCR signaling.

Název v anglickém jazyce

Clustering of the zeta-Chain Can Initiate T Cell Receptor Signaling

Popis výsledku anglicky

T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of zeta -chain in a light controlled manner. We showed that spatial clustering of the zeta -chain intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of zeta -chain, Zap70, PLC gamma, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate zeta -chain phosphorylation upon zeta -chain clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed zeta -chain clusters at the plasma membrane. Taken together, our data demonstrated the biophysical relevance of receptor clustering in TCR signaling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences [online]

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

25

Strana od-do

3498

Kód UT WoS článku

000539312100094

EID výsledku v databázi Scopus

2-s2.0-85084963728