دورية أكاديمية
Trichoplein binds PCM1 and controls endothelial cell function by regulating autophagy
| العنوان: | Trichoplein binds PCM1 and controls endothelial cell function by regulating autophagy |
|---|---|
| المؤلفون: | Martello, Andrea, Lauriola, Angela, Mellis, David, Parish, Elisa, Dawson, John C, Imrie, Lisa, Vidmar, Martina, Gammoh, Noor, Mitić, Tijana, Brittan, Mairi, Mills, Nicholas L, Carragher, Neil O, D'Arca, Domenico, Caporali, Andrea |
| المساهمون: | Martello, Andrea, Lauriola, Angela, Mellis, David, Parish, Elisa, Dawson, John C, Imrie, Lisa, Vidmar, Martina, Gammoh, Noor, Mitić, Tijana, Brittan, Mairi, Mills, Nicholas L, Carragher, Neil O, D'Arca, Domenico, Caporali, Andrea |
| سنة النشر: | 2020 |
| المجموعة: | Università degli Studi di Verona: Catalogo dei Prodotti della Ricerca (IRIS) |
| مصطلحات موضوعية: | GABARAP, SQSTM1/p62, autophagy, centriolar satellites, endothelial cells |
| الوصف: | Autophagy is an essential cellular quality control process that has emerged as a critical one for vascular homeostasis. Here, we show that trichoplein (TCHP) links autophagy with endothelial cell (EC) function.TCHPlocalizes to centriolar satellites, where it binds and stabilizesPCM1. Loss ofTCHPleads to delocalization and proteasome-dependent degradation ofPCM1, further resulting in degradation ofPCM1's binding partnerGABARAP. Autophagic flux under basal conditions is impaired inTHCP-depletedECs, andSQSTM1/p62 (p62) accumulates. We further show thatTCHPpromotes autophagosome maturation and efficient clearance of p62 within lysosomes, without affecting their degradative capacity. ReducedTCHPand high p62 levels are detected in primaryECs from patients with coronary artery disease. This phenotype correlates with impairedECfunction and can be ameliorated byNF-kappa Binhibition. Moreover, Tchp knock-out mice accumulate of p62 in the heart and cardiac vessels correlating with reduced cardiac vascularization. Taken together, our data reveal thatTCHPregulates endothelial cell function via an autophagy-mediated mechanism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32337819; info:eu-repo/semantics/altIdentifier/wos/WOS:000528587500001; volume:21; issue:7; firstpage:e48192; lastpage:1; numberofpages:16; journal:EMBO REPORTS; https://hdl.handle.net/11562/1116956Test |
| DOI: | 10.15252/embr.201948192 |
| الإتاحة: | https://doi.org/10.15252/embr.201948192Test https://hdl.handle.net/11562/1116956Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7CA59DB6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/embr.201948192 |
|---|