Hilu-Dadia Reut, Ghanem Aseel, Vogelesang Shelly, Ayoub Malak, Hakim-Mishnaevski Ketty, Kurant Estee
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel.
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel.
Cell Rep. 2025 Jan 28;44(1):115201. doi: 10.1016/j.celrep.2024.115201. Epub 2025 Jan 10.
The elimination of superfluous neurons via apoptosis and subsequent glial phagocytosis is crucial for the development of the central nervous system (CNS). In Drosophila, two glial phagocytic receptors, six-microns-under (SIMU) and Draper, mediate the phagocytosis of apoptotic neurons during embryogenesis. However, in simu;draper double-mutant embryos, some apoptotic neurons are still engulfed by the glia, suggesting the involvement of additional receptors. Here, we discover the Drosophila CD36 homolog Santa-maria, a transmembrane receptor, which is specifically expressed in embryonic phagocytic glia and plays a major role in the recognition and engulfment steps of phagocytosis. Our data demonstrate that santa-maria genetically interacts with simu and draper, while the protein product binds apoptotic cells and physically interacts with the SIMU protein. Moreover, we reveal that triple knockout of genes for all three glial phagocytic receptors (i.e., simu, draper, and santa-maria) causes partial lethality, thus illuminating their role in development, particularly in the developing nervous system.
通过凋亡和随后的胶质细胞吞噬作用消除多余的神经元对于中枢神经系统（CNS）的发育至关重要。在果蝇中，两种胶质细胞吞噬受体，六微米下（SIMU）和德雷珀（Draper），在胚胎发育过程中介导凋亡神经元的吞噬作用。然而，在simu;draper双突变胚胎中，一些凋亡神经元仍然被胶质细胞吞噬，这表明存在其他受体的参与。在这里，我们发现了果蝇CD36同源物圣玛丽亚，一种跨膜受体，它在胚胎吞噬性胶质细胞中特异性表达，并在吞噬作用的识别和吞噬步骤中起主要作用。我们的数据表明，圣玛丽亚与simu和draper发生基因相互作用，而其蛋白质产物结合凋亡细胞并与SIMU蛋白发生物理相互作用。此外，我们发现所有三种胶质细胞吞噬受体（即simu、draper和圣玛丽亚）的基因三重敲除会导致部分致死性，从而阐明了它们在发育中的作用，特别是在发育中的神经系统中的作用。
