Related Experiment Video
Updated: Feb 6, 2026
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Spatial control of Draper receptor signaling initiates apoptotic cell engulfment
Adam P Williamson1,2, Ronald D Vale3,2
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA.
Abstract:
The engulfment of apoptotic cells is essential for tissue homeostasis and recovering from damage. Engulfment is mediated by receptors that recognize ligands exposed on apoptotic cells such as phosphatidylserine (PS). In this study, we convert Drosophila melanogaster S2 cells into proficient phagocytes by transfecting the Draper engulfment receptor and replacing apoptotic cells with PS-coated beads. Similar to the T cell receptor (TCR), PS-ligated Draper forms dynamic microclusters that recruit cytosolic effector proteins and exclude a bulky transmembrane phosphatase, consistent with a kinetic segregation-based triggering mechanism. However, in contrast with the TCR, localized signaling at Draper microclusters results in time-dependent depletion of actin filaments, which facilitates engulfment. The Draper-PS extracellular module can be replaced with FRB and FKBP, respectively, resulting in a rapamycin-inducible engulfment system that can be programmed toward defined targets. Collectively, our results reveal mechanistic similarities and differences between the receptors involved in apoptotic corpse clearance and mammalian immunity and demonstrate that engulfment can be reprogrammed toward nonnative targets.
Insights
Scientists reprogrammed cell engulfment, essential for tissue repair, by engineering receptors to target specific materials. This discovery offers new insights into cellular mechanisms and potential therapeutic applications.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Cellular engulfment, or phagocytosis, is critical for tissue homeostasis and damage repair.
- Receptors recognizing phosphatidylserine (PS) on apoptotic cells mediate this process.
- Understanding engulfment mechanisms is key to regenerative medicine and immunology.
Purpose of the Study:
- To investigate the mechanisms of apoptotic cell engulfment mediated by the Draper receptor in *Drosophila* S2 cells.
- To explore the potential for reprogramming cellular engulfment pathways for targeted applications.
Main Methods:
- Transfected *Drosophila* S2 cells with the Draper engulfment receptor.
- Utilized PS-coated beads as a model for apoptotic cells.
- Investigated Draper microcluster dynamics and signaling pathways.
- Engineered a rapamycin-inducible system using FRB and FKBP domains.
Main Results:
- PS-ligated Draper formed dynamic microclusters, similar to the T cell receptor (TCR), recruiting effector proteins.
- Engulfment involved time-dependent actin filament depletion, facilitating the process.
- A rapamycin-inducible system allowed programmed engulfment toward defined targets.
Conclusions:
- Mechanistic similarities and differences exist between apoptotic clearance receptors and mammalian immune receptors.
- Cellular engulfment can be reprogrammed to target non-native materials, opening new avenues for research and therapy.
Related Concept Videos
02:03What is Cell Signaling?
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:21Cell-surface Signaling
01:41Signal Sequences and Sorting Receptors
01:28Insulin: The Receptor and Signaling Pathways
02:33Initiation of Translation
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...