Matches in SemOpenAlex for { <https://semopenalex.org/work/W3133434270> ?p ?o ?g. }
- W3133434270 abstract "Podocytes are key to the glomerular filtration barrier by forming a slit diaphragm between interdigitating foot processes; however, the molecular details and functional importance of protein folding and degradation in the ER remain unknown. Here, we show that the SEL1L-HRD1 protein complex of ER-associated degradation (ERAD) is required for slit diaphragm formation and glomerular filtration function. SEL1L-HRD1 ERAD is highly expressed in podocytes of both mouse and human kidneys. Mice with podocyte-specific Sel1L deficiency develop podocytopathy and severe congenital nephrotic syndrome with an impaired slit diaphragm shortly after weaning and die prematurely, with a median lifespan of approximately 3 months. We show mechanistically that nephrin, a type 1 membrane protein causally linked to congenital nephrotic syndrome, is an endogenous ERAD substrate. ERAD deficiency attenuated the maturation of nascent nephrin, leading to its retention in the ER. We also show that various autosomal-recessive nephrin disease mutants were highly unstable and broken down by SEL1L-HRD1 ERAD, which attenuated the pathogenicity of the mutants toward the WT allele. This study uncovers a critical role of SEL1L-HRD1 ERAD in glomerular filtration barrier function and provides insights into the pathogenesis associated with autosomal-recessive disease mutants." @default.
- W3133434270 created "2021-03-01" @default.
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- W3133434270 date "2021-04-01" @default.
- W3133434270 modified "2023-10-12" @default.
- W3133434270 title "Endoplasmic reticulum–associated degradation is required for nephrin maturation and kidney glomerular filtration function" @default.
- W3133434270 cites W1532265252 @default.
- W3133434270 cites W1922472632 @default.
- W3133434270 cites W1964532554 @default.
- W3133434270 cites W1965197568 @default.
- W3133434270 cites W1988364921 @default.
- W3133434270 cites W1990488096 @default.
- W3133434270 cites W1998399313 @default.
- W3133434270 cites W2005039062 @default.
- W3133434270 cites W2023251227 @default.
- W3133434270 cites W2025226894 @default.
- W3133434270 cites W2027706325 @default.
- W3133434270 cites W2031085640 @default.
- W3133434270 cites W2033798110 @default.
- W3133434270 cites W2035349696 @default.
- W3133434270 cites W2046540619 @default.
- W3133434270 cites W2090294867 @default.
- W3133434270 cites W2091652646 @default.
- W3133434270 cites W2097300515 @default.
- W3133434270 cites W2102360423 @default.
- W3133434270 cites W2107179956 @default.
- W3133434270 cites W2107780546 @default.
- W3133434270 cites W2109222531 @default.
- W3133434270 cites W2110230080 @default.
- W3133434270 cites W2113856093 @default.
- W3133434270 cites W2115197028 @default.
- W3133434270 cites W2122345674 @default.
- W3133434270 cites W2126440245 @default.
- W3133434270 cites W2129416468 @default.
- W3133434270 cites W2129649143 @default.
- W3133434270 cites W2131355460 @default.
- W3133434270 cites W2133024527 @default.
- W3133434270 cites W2133176024 @default.
- W3133434270 cites W2134983755 @default.
- W3133434270 cites W2137667514 @default.
- W3133434270 cites W2145174769 @default.
- W3133434270 cites W2153458899 @default.
- W3133434270 cites W2153534186 @default.
- W3133434270 cites W2158424828 @default.
- W3133434270 cites W2161748321 @default.
- W3133434270 cites W2163543028 @default.
- W3133434270 cites W2168450345 @default.
- W3133434270 cites W2169883398 @default.
- W3133434270 cites W2174130773 @default.
- W3133434270 cites W2181477489 @default.
- W3133434270 cites W2256655918 @default.
- W3133434270 cites W2282594374 @default.
- W3133434270 cites W2387614496 @default.
- W3133434270 cites W2441416563 @default.
- W3133434270 cites W2467855616 @default.
- W3133434270 cites W2514806077 @default.
- W3133434270 cites W2525587647 @default.
- W3133434270 cites W2580169875 @default.
- W3133434270 cites W2606110324 @default.
- W3133434270 cites W2755265275 @default.
- W3133434270 cites W2764162783 @default.
- W3133434270 cites W2788091697 @default.
- W3133434270 cites W2806867311 @default.
- W3133434270 cites W2807661081 @default.
- W3133434270 cites W2809543651 @default.
- W3133434270 cites W2811301994 @default.
- W3133434270 cites W2889264661 @default.
- W3133434270 cites W2898831421 @default.
- W3133434270 cites W2899448135 @default.
- W3133434270 cites W2908610713 @default.
- W3133434270 cites W2949559283 @default.
- W3133434270 cites W2954849799 @default.
- W3133434270 cites W2966057938 @default.
- W3133434270 cites W2979549406 @default.
- W3133434270 cites W2991437291 @default.
- W3133434270 cites W3011224064 @default.
- W3133434270 cites W3012252561 @default.