دورية أكاديمية
Biallelic loss of human CTNNA2, encoding alpha N-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration
| العنوان: | Biallelic loss of human CTNNA2, encoding alpha N-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration |
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| المؤلفون: | Schaffer, Ashleigh E., Breuss, Martin W., Caglayan, Ahmet Okay, Al-Sanaa, Nouriya, Al-Abdulwahed, Hind Y., Kaymakcalan, Hande, Yilmaz, Cahide, Zaki, Maha S., Rosti, Rasim O., Copeland, Brett, Baek, Seung Tae, Musaev, Damir, Scott, Eric C., Ben-Omran, Tawfeg, Kariminejad, Ariana, Kayserili, Hulya, Mojahedi, Faezeh, Kara, Majdi, Cai, Na, Silhavy, Jennifer L., Elsharif, Seham, Fenercioglu, Elif, Barshop, Bruce A., Kara, Bulent, Wang, Rengang, Stanley, Valentina, James, Kiely N., Nachnani, Rahul, Kalur, Aneesha, Megahed, Hisham, Incecik, Faruk, Danda, Sumita, Alanay, Yasemin, Faqeih, Eissa, Melikishvili, Gia, Mansour, Lobna, Miller, Ian, Sukhudyan, Biayna, Chelly, Jamel, Dobyns, William B., Bilguvar, Kaya, Abou Jamra, Rami, Gunel, Murat, Gleeson, Joseph G. |
| بيانات النشر: | NATURE PUBLISHING GROUP |
| سنة النشر: | 2018 |
| المجموعة: | Acibadem University Repository |
| الوصف: | Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding alpha N-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss in neurons led to defects in neurite stability and migration. The alpha N-catenin paralog, alpha E-catenin, acts as a switch regulating the balance between beta-catenin and Arp2/3 actin filament activities(1). Loss of alpha N-catenin did not affect beta-catenin signaling, but recombinant alpha N-catenin interacted with purified actin and repressed ARP2/3 actin-branching activity. The actin-binding domain of alpha N-catenin or ARP2/3 inhibitors rescued the neuronal phenotype associated with CTNNA2 loss, suggesting ARP2/3 de-repression as a potential disease mechanism. Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons. ; 8 ; AUG ; 1093+ ; 50 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | NATURE GENETICS; https://hdl.handle.net/11443/2823Test; http://dx.doi.org/10.1038/s41588-018-0166-0Test; WOS:000440423400008 |
| DOI: | 10.1038/s41588-018-0166-0 |
| الإتاحة: | https://doi.org/10.1038/s41588-018-0166-0Test https://hdl.handle.net/11443/2823Test |
| رقم الانضمام: | edsbas.B0B21BB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41588-018-0166-0 |
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