Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00637010" target="_blank" >RIV/67985904:_____/25:00637010 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/25:00637010 RIV/00216224:14110/25:00141289 RIV/65269705:_____/25:00081969

Výsledek na webu

<a href="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02208-w" target="_blank" >https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02208-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12964-025-02208-w" target="_blank" >10.1186/s12964-025-02208-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors

Popis výsledku v původním jazyce

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress, impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

Název v anglickém jazyce

Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors

Popis výsledku anglicky

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress, impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Cell communication and signaling : CCS

ISSN

1478-811X

e-ISSN

1478-811X

Svazek periodika

23

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

209

Kód UT WoS článku

001479437500002

EID výsledku v databázi Scopus

2-s2.0-105003875911