Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function
Abstract
Using forward genetic analysis, we identified a previously unknown regulator of mouse lymphopoiesis, RABL3. The small GTPase RABL3 is also necessary for embryonic development. We found that GPR89, a putative GPCR or ion channel, interacts with, and is stabilized by, RABL3, and mice with hypomorphic mutations in either protein displayed B cell and T cell deficiencies. We crystallized RABL3 and showed it forms a homodimer with subunits similar to other small G proteins. However, the conformation of mutated RABL3 is abnormal and may disrupt effector binding. Critical proteins that control hematopoiesis remain to be discovered, and RABL3 is one such example.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- April 2020
- DOI:
- 10.1073/pnas.2000703117
- Bibcode:
- 2020PNAS..117.8563Z