Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Hypomorphic human SEL1L and HRD1 variants uncouple multilayered ER- associated degradation machinery
Ist Teil von
The Journal of clinical investigation, 2024-01, Vol.134 (2)
Ort / Verlag
American Society for Clinical Investigation
Erscheinungsjahr
2024
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
The suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1LHRD1) complex of the endoplasmic reticulum-associated degradation (ERAD) machinery is a key cellular proteostasis pathway. Although previous studies have shown ERAD as promoting the development and maintenance of many cell types in mice, its importance to human physiology remained undetermined. In two articles in this issue of theJCI, Qi and colleagues describe four biallelic hypomorphic SEL1L and HRD1 variants that were associated with neurodevelopment disorders, locomotor dysfunction, impaired immunity, and premature death in patients. These pathogenic SEL1L-HRD1 variants shine a light on the critical importance of ERAD in humans and pave the way for future studies dissecting ERAD mechanisms in specific cell types.