التفاصيل البيبلوغرافية
| العنوان: |
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination |
| المؤلفون: |
Chen, Chun-Chin, Chen, Bo-Ruei, Wang, Yinan, Curman, Philip, Beilinson, Helen A., Brecht, Ryan M., Liu, Catherine C., Farrell, Ryan J., de Juan-Sanz, Jaime, Charbonnier, Louis-Marie, Kajimura, Shingo, Ryan, Timothy A., Schatz, David G., Chatila, Talal A., Wikstrom, Jakob D., Tyler, Jessica K., Sleckman, Barry P. |
| المساهمون: |
Leukemia & Lymphoma Society, National Institutes of Health, Vetenskapsrådet, Hudfonden, Svenska Sällskapet förr Medicinsk Forskning, ALF Medicin Stockholm, Jeanssons Stiftelser, Tore Nilssons Stiftelse |
| المصدر: |
Journal of Experimental Medicine ; volume 218, issue 8 ; ISSN 0022-1007 1540-9538 |
| بيانات النشر: |
Rockefeller University Press |
| سنة النشر: |
2021 |
| الوصف: |
A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding the Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from the cytosol into the ER lumen to maintain the ER Ca2+ reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads to reduced V(D)J recombination kinetics due to diminished RAG-mediated DNA cleavage. SERCA2 deficiency in B cells leads to increased expression of SERCA3, and combined loss of SERCA2 and SERCA3 results in decreased ER Ca2+ levels, increased cytosolic Ca2+ levels, reduction in RAG1 and RAG2 gene expression, and a profound block in V(D)J recombination. Mice with B cells deficient in SERCA2 and humans with Darier disease, caused by heterozygous ATP2A2 mutations, have reduced numbers of mature B cells. We conclude that SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination and that defects in SERCA functions cause lymphopenia. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1084/jem.20201708 |
| DOI: |
10.1084/jem.20201708/1816228/jem_20201708.pdf |
| الإتاحة: |
https://doi.org/10.1084/jem.20201708Test |
| حقوق: |
http://www.rupress.org/termsTest/ ; https://creativecommons.org/licenses/by-nc-sa/4.0Test/ |
| رقم الانضمام: |
edsbas.CCDDFE53 |
| قاعدة البيانات: |
BASE |
