TMED3 Complex Mediates ER Stress-Associated Secretion of CFTR, Pendrin, and SARS-CoV-2 Spike.
Adv Sci (Weinh)
; 9(24): e2105320, 2022 08.
Article
in English
| MEDLINE | ID: covidwho-1905773
ABSTRACT
Under ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi-independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress-associated UPS of transmembrane proteins. The gene silencing results reveal that TMED2, TMED3, TMED9 and TMED10 are involved in the UPS of transmembrane proteins, such as CFTR, pendrin and SARS-CoV-2 Spike. Subsequent mechanistic analyses indicate that TMED3 recognizes the ER core-glycosylated protein cargos and that the heteromeric TMED2/3/9/10 complex mediates their UPS. Co-expression of all four TMEDs improves, while each single expression reduces, the UPS and ion transport function of trafficking-deficient ΔF508-CFTR and p.H723R-pendrin, which cause cystic fibrosis and Pendred syndrome, respectively. In contrast, TMED2/3/9/10 silencing reduces SARS-CoV-2 viral release. These results provide evidence for a common role of TMED3 and related TMEDs in the ER stress-associated, Golgi-independent secretion of transmembrane proteins.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cystic Fibrosis Transmembrane Conductance Regulator
/
Endoplasmic Reticulum Stress
/
Spike Glycoprotein, Coronavirus
/
Sulfate Transporters
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Adv Sci (Weinh)
Year:
2022
Document Type:
Article
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