| First Author | Agthe M | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 1 | Pages | 10-18.e5 |
| PubMed ID | 30282020 | Mgi Jnum | J:270405 |
| Mgi Id | MGI:6278456 | Doi | 10.1016/j.celrep.2018.09.005 |
| Citation | Agthe M, et al. (2018) Mutations in Craniosynostosis Patients Cause Defective Interleukin-11 Receptor Maturation and Drive Craniosynostosis-like Disease in Mice. Cell Rep 25(1):10-18.e5 |
| abstractText | Premature closure of the sutures that connect the cranial bones during development of the mammalian skull results in a phenotype called craniosynostosis. Recently, several craniosynostosis patients with missense mutations within the gene encoding the interleukin-11 receptor (IL-11R) have been described, but the underlying molecular mechanisms have remained elusive. IL-11 is a cytokine that has a crucial role in bone remodeling and activates cells via binding to the IL-11R. Here, we show that patient mutations prevented maturation of the IL-11R, resulting in endoplasmic reticulum retention and diminished cell surface appearance. Disruption of a conserved tryptophan-arginine zipper within the third domain of the IL-11R was the underlying cause of the defective maturation. IL-11 classic signaling via the membrane-bound receptor, but not IL-11 trans-signaling via the soluble receptor, was the crucial pathway for normal skull development in mice in vivo. Thus, the specific therapeutic inhibition of IL-11 trans-signaling does not interfere with skull development. |
