| First Author | Nair-Gill E | Year | 2021 |
| Journal | EMBO J | Volume | 40 |
| Issue | 9 | Pages | e104888 |
| PubMed ID | 33630350 | Mgi Jnum | J:320993 |
| Mgi Id | MGI:6729769 | Doi | 10.15252/embj.2020104888 |
| Citation | Nair-Gill E, et al. (2021) Calcium flux control by Pacs1-Wdr37 promotes lymphocyte quiescence and lymphoproliferative diseases. EMBO J 40(9):e104888 |
| abstractText | Endoplasmic reticulum (ER) calcium (Ca(2+) ) stores are critical to proteostasis, intracellular signaling, and cellular bioenergetics. Through forward genetic screening in mice, we identified two members of a new complex, Pacs1 and Wdr37, which are required for normal ER Ca(2+) handling in lymphocytes. Deletion of Pacs1 or Wdr37 caused peripheral lymphopenia that was linked to blunted Ca(2+) release from the ER after antigen receptor stimulation. Pacs1-deficient cells showed diminished inositol triphosphate receptor expression together with increased ER and oxidative stress. Mature Pacs1(-/-) B cells proliferated and died in vivo under lymphocyte replete conditions, indicating spontaneous loss of cellular quiescence. Disruption of Pacs1-Wdr37 did not diminish adaptive immune responses, but potently suppressed lymphoproliferative disease models by forcing loss of quiescence. Thus, Pacs1-Wdr37 plays a critical role in stabilizing lymphocyte populations through ER Ca(2+) handling and presents a new target for lymphoproliferative disease therapy. |
