دورية أكاديمية
Chorein-sensitive polymerization of cortical actin and suicidal cell death in chorea-acanthocytosis.
| العنوان: | Chorein-sensitive polymerization of cortical actin and suicidal cell death in chorea-acanthocytosis. |
|---|---|
| المؤلفون: | Föller, Michael, Hermann, Andreas, Schöls, Ludger, Lerche, Holger, Stournaras, Christos, Storch, Alexander, Lang, Florian, Gu, Shuchen, Alesutan, Ioana, Qadri, Syed M, Borst, Oliver, Schmidt, Eva-Maria, Schiele, Franziska, vom Hagen, Jennifer Müller, Saft, Carsten |
| المصدر: | The FASEB journal 26(4), 1526-1534 (2012). doi:10.1096/fj.11-198317 |
| بيانات النشر: | FASEB |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/570, Acanthocytes: cytology, Acanthocytes: metabolism, Actins: metabolism, Adult, Aged, Animals, Apoptosis: physiology, Erythrocytes: cytology, Erythrocytes: metabolism, Female, Gene Silencing, Humans, K562 Cells, Male, Middle Aged, Mutation, Neuroacanthocytosis: genetics, Neuroacanthocytosis: pathology, Neuroacanthocytosis: physiopathology, Phosphatidylinositol 3-Kinases: genetics, Phosphatidylinositol 3-Kinases: metabolism, Vesicular Transport Proteins: genetics, Vesicular Transport Proteins: metabolism, Young Adult, bcl-Associated Death Protein: genetics, bcl-Associated Death Protein: metabolism, p21-Activated Kinases: genetics, p21-Activated Kinases: metabolism, rac1 GTP-Binding Protein: genetics |
| جغرافية الموضوع: | DE |
| الوصف: | Chorea-acanthocytosis is an inevitably lethal genetic disease characterized by a progressive hyperkinetic movement disorder and cognitive and behavioral abnormalities as well as acanthocytosis. The disease is caused by loss-of-function mutations of the gene encoding vacuolar protein sorting-associated protein 13A (VPS13A) or chorein, a protein with unknown function expressed in various cell types. How chorein deficiency leads to the pathophysiology of chorea-acanthocytosis remains enigmatic. Here we show decreased phosphoinositide-3-kinase (PI3K)-p85-subunit phosphorylation, ras-related C3 botulinum toxin substrate 1 (Rac1) activity, and p21 protein-activated kinase 1 (PAK1) phosphorylation as well as depolymerized cortical actin in erythrocytes from patients with chorea-acanthocytosis and in K562-erythrocytic cells following chorein silencing. Pharmacological inhibition of PI3K, Rac1, or PAK1 similarly triggered actin depolymerization. Moreover, in K562 cells, both chorein silencing and PAK1 inhibition with IPA-3 decreased phosphorylation of Bad, a Bcl2-associated protein, promoting apoptosis by forming mitochondrial pores, followed by mitochondrial depolarization, DNA fragmentation, and phosphatidylserine exposure at the cell surface, all hallmarks of apoptosis. Our observations reveal chorein as a novel powerful regulator of cytoskeletal architecture and cell survival, thus explaining erythrocyte misshape and possibly neurodegeneration in chorea-acanthocytosis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/pmid:22227296; info:eu-repo/semantics/altIdentifier/issn/1530-6860; info:eu-repo/semantics/altIdentifier/issn/0892-6638; https://pub.dzne.de/record/136474Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-02796%22Test |
| الإتاحة: | https://doi.org/10.1096/fj.11-198317Test https://pub.dzne.de/record/136474Test https://pub.dzne.de/search?p=id:%22DZNE-2020-02796%22Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.272ED67C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |