Post translational modification of CSF1R as a mechanism for ligand preference
Faculty Mentor
Jason W Ashley
Presentation Type
Poster
Start Date
5-8-2024 11:15 AM
End Date
5-8-2024 1:00 PM
Location
PUB NCR
Primary Discipline of Presentation
Biology
Abstract
Macrophages are immune cells that help provide the first line of defense against a wide range of internal and external insults and create the bridge between innate and adaptive immune responses. When macrophage homeostasis is disrupted disease states occur. Associated disease states include rheumatoid arthritis, osteoporosis, and multiple sclerosis which can severely affect quality of life for those affected. The survival and proliferation of macrophages is largely controlled by signaling through colony stimulating factor 1 receptor (CSF1R). Notably, this receptor can be activated by two non-homologous ligands, colony stimulating factor 1 (CSF1) and interleukin-34 (IL34). These two ligands are differentially required for macrophage homeostasis across body systems and have different associated pathologies. The ability to separately influence these ligands could provide a novel therapeutic target for these diseases. While the differential effects of CSF1Rs dual ligands have been demonstrated, the structural mechanisms leading to these effects are well understood. In our work we have found that IL-34 appears to only bind the smaller glycoprotein 130kD (gp130) version of the CSF1R receptor while CSF1 appears to bind both gp130 and the larger glycoprotein 150kD (gp150) forms of the receptor. This provides a novel explanation for the differential signaling and binding affinity seen between the ligands. We are additionally investigating the potential role of sialic acid, a negatively charged sugar that is added to CSF1R, in influencing this difference in binding affinity.
Recommended Citation
Beaulaurier, Eric J. and Ashley, Jason W., "Post translational modification of CSF1R as a mechanism for ligand preference" (2024). 2024 Symposium. 22.
https://dc.ewu.edu/srcw_2024/ps_2024/p2_2024/22
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Post translational modification of CSF1R as a mechanism for ligand preference
PUB NCR
Macrophages are immune cells that help provide the first line of defense against a wide range of internal and external insults and create the bridge between innate and adaptive immune responses. When macrophage homeostasis is disrupted disease states occur. Associated disease states include rheumatoid arthritis, osteoporosis, and multiple sclerosis which can severely affect quality of life for those affected. The survival and proliferation of macrophages is largely controlled by signaling through colony stimulating factor 1 receptor (CSF1R). Notably, this receptor can be activated by two non-homologous ligands, colony stimulating factor 1 (CSF1) and interleukin-34 (IL34). These two ligands are differentially required for macrophage homeostasis across body systems and have different associated pathologies. The ability to separately influence these ligands could provide a novel therapeutic target for these diseases. While the differential effects of CSF1Rs dual ligands have been demonstrated, the structural mechanisms leading to these effects are well understood. In our work we have found that IL-34 appears to only bind the smaller glycoprotein 130kD (gp130) version of the CSF1R receptor while CSF1 appears to bind both gp130 and the larger glycoprotein 150kD (gp150) forms of the receptor. This provides a novel explanation for the differential signaling and binding affinity seen between the ligands. We are additionally investigating the potential role of sialic acid, a negatively charged sugar that is added to CSF1R, in influencing this difference in binding affinity.
