Determining the Upstream Ligand for Draper in Cortex Glial Engulfment

Conference Year

January 2019

Abstract

Microglia have been systematically identified as the primary resident CNS macrophage, shown to engulf dead cells, cellular debris, and synapses. Previous studies have identified a role for the classical complement cascade in glial engulfment (Iram et al., 2016). In Drosophila, cortex glia play an analogous role in the engulfment of dead and dying neurons. Draper—the principal player in the activation of Drosophila glial engulfment—is the homolog of mammalian MegF10, which acts as the receptor for the complement protein C1q to regulate the clearance of apoptotic cells (Iram et al., 2016). Interestingly, only two Draper ligands have been identified in Drosophila. Mcr, the Drosophila complement homolog, is a known draper ligand in salivary glands (Lin et al., 2017). Additionally, Pretaporter has been shown to bind to Draper in hemocytes and macrophages and has been eluded to as a Draper ligand in embryonic glial engulfment (Kuraishi et al., 2009). Currently, the upstream activator for Draper in cortex glial engulfment is unknown; therefore, we do not fully understand how it recognizes and clears cell death. The relationship between Draper and the mammalian MegF10, as well as its known ligands, has prompted us to explore which of these proteins—Mcr or Pretaporter—is primarily responsible for the induction of phagocytosis in cortex glia.

References:

Iram, T., Ramirez-Ortiz, Z., Byrne, M. H., Coleman, U. A., Kingery, N. D., Means, T. K., . . . Khoury, J. E. (2016). Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes. The Journal of Neuroscience, 36(19), 5185-5192. doi:10.1523/jneurosci.3850-15.2016

Lin, L., Rodrigues, F. S., Kary, C., Contet, A., Logan, M., Baxter, R. H., . . . Baehrecke, E. H. (2017). Complement-Related Regulates Autophagy in Neighboring Cells. Cell, 170(1). doi:10.1016/j.cell.2017.06.018

Kuraishi, T., Nakagawa, Y., Nagaosa, K., Hashimoto, Y., Ishimoto, T., Moki, T., . . . Nakanishi, Y. (2009). Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells. The EMBO Journal, 28(24), 3868-3878. doi:10.1038/emboj.2009.343

Primary Faculty Mentor Name

Jaeda Coutinho-Budd

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Biological Sciences

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Determining the Upstream Ligand for Draper in Cortex Glial Engulfment

Microglia have been systematically identified as the primary resident CNS macrophage, shown to engulf dead cells, cellular debris, and synapses. Previous studies have identified a role for the classical complement cascade in glial engulfment (Iram et al., 2016). In Drosophila, cortex glia play an analogous role in the engulfment of dead and dying neurons. Draper—the principal player in the activation of Drosophila glial engulfment—is the homolog of mammalian MegF10, which acts as the receptor for the complement protein C1q to regulate the clearance of apoptotic cells (Iram et al., 2016). Interestingly, only two Draper ligands have been identified in Drosophila. Mcr, the Drosophila complement homolog, is a known draper ligand in salivary glands (Lin et al., 2017). Additionally, Pretaporter has been shown to bind to Draper in hemocytes and macrophages and has been eluded to as a Draper ligand in embryonic glial engulfment (Kuraishi et al., 2009). Currently, the upstream activator for Draper in cortex glial engulfment is unknown; therefore, we do not fully understand how it recognizes and clears cell death. The relationship between Draper and the mammalian MegF10, as well as its known ligands, has prompted us to explore which of these proteins—Mcr or Pretaporter—is primarily responsible for the induction of phagocytosis in cortex glia.

References:

Iram, T., Ramirez-Ortiz, Z., Byrne, M. H., Coleman, U. A., Kingery, N. D., Means, T. K., . . . Khoury, J. E. (2016). Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes. The Journal of Neuroscience, 36(19), 5185-5192. doi:10.1523/jneurosci.3850-15.2016

Lin, L., Rodrigues, F. S., Kary, C., Contet, A., Logan, M., Baxter, R. H., . . . Baehrecke, E. H. (2017). Complement-Related Regulates Autophagy in Neighboring Cells. Cell, 170(1). doi:10.1016/j.cell.2017.06.018

Kuraishi, T., Nakagawa, Y., Nagaosa, K., Hashimoto, Y., Ishimoto, T., Moki, T., . . . Nakanishi, Y. (2009). Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells. The EMBO Journal, 28(24), 3868-3878. doi:10.1038/emboj.2009.343