Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages
Sandra Sofía Edwards-Jorquera1, Floris Bosveld2, Yohanns A Bellaïche2
1Centro de Regulación del Genoma, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Abstract:
Phagocytes use their actomyosin cytoskeleton to migrate as well as to probe their environment by phagocytosis or macropinocytosis. Although migration and extracellular material uptake have been shown to be coupled in some immune cells, the mechanisms involved in such coupling are largely unknown. By combining time-lapse imaging with genetics, we here identify the lysosomal Ca2+ channel Trpml as an essential player in the coupling of cell locomotion and phagocytosis in hemocytes, the Drosophila macrophage-like immune cells. Trpml is needed for both hemocyte migration and phagocytic processing at distinct subcellular localizations: Trpml regulates hemocyte migration by controlling actomyosin contractility at the cell rear, whereas its role in phagocytic processing lies near the phagocytic cup in a myosin-independent fashion. We further highlight that Vamp7 also regulates phagocytic processing and locomotion but uses pathways distinct from those of Trpml. Our results suggest that multiple mechanisms may have emerged during evolution to couple phagocytic processing to cell migration and facilitate space exploration by immune cells.
Insights
The lysosomal calcium channel Trpml (Transient Receptor Potential Mucolipin) is crucial for linking immune cell movement and phagocytosis. It controls actomyosin contractility for migration and aids in phagocytic processing near the cell membrane.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Phagocytes, like macrophages, utilize their actomyosin cytoskeleton for migration and engulfing materials (phagocytosis/macropinocytosis).
- The precise mechanisms coupling cell migration and extracellular material uptake in immune cells remain largely unelucidated.
Purpose of the Study:
- To identify key molecular players involved in coupling cell locomotion and phagocytosis in Drosophila hemocytes.
- To elucidate the distinct subcellular roles of identified molecules in migration and phagocytic processing.
Main Methods:
- Utilized time-lapse imaging to observe cellular dynamics.
- Employed genetic approaches to investigate gene function in Drosophila hemocytes.
Main Results:
- Identified the lysosomal calcium channel Trpml (Transient Receptor Potential Mucolipin) as essential for coupling hemocyte migration and phagocytosis.
- Trpml regulates hemocyte migration via actomyosin contractility at the cell rear.
- Trpml functions in a myosin-independent manner near the phagocytic cup for phagocytic processing.
- Vamp7 also influences phagocytic processing and locomotion through distinct pathways.
Conclusions:
- Trpml plays dual, spatially distinct roles in regulating immune cell migration and phagocytic efficiency.
- Multiple evolutionary mechanisms likely exist to coordinate phagocytic processing with cell migration for immune surveillance.
- This study provides novel insights into the molecular basis of immune cell motility and environmental interaction.
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