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L-Plastin promotes podosome longevity and supports macrophage motility
Julie Y Zhou1, Taylor P Szasz1, Phillip J Stewart-Hutchinson1
1Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Abstract:
Elucidating the molecular regulation of macrophage migration is essential for understanding the pathophysiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL-/- mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL-/- mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility.
Insights
The actin-bundling protein l-plastin (LPL) is crucial for macrophage motility. Loss of LPL disrupts podosome stability and impairs macrophage elongation, hindering migration in response to infection and autoimmune conditions.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Macrophage migration is vital for host defense and implicated in diseases like infections and autoimmune disorders.
- Macrophage movement relies on actin cytoskeleton dynamics, including podosomes and lamellipodia formation.
- The actin-bundling protein l-plastin (LPL) is a potential regulator of these cellular processes.
Purpose of the Study:
- To investigate the function of l-plastin (LPL) in primary macrophage migration and actin dynamics.
- To elucidate the role of LPL in the stability of podosomes and macrophage elongation.
- To determine the impact of LPL deficiency on macrophage transmigration and in vivo monocyte recruitment.
Main Methods:
- Utilized LPL-deficient (LPL-/-) mice and wild-type controls.
- Employed live-cell imaging of F-actin in primary resident peritoneal macrophages.
- Assessed podosome stability, macrophage elongation, and transmigration in vitro and in vivo.
Main Results:
- LPL deficiency resulted in disrupted podosome stability, characterized by decreased longevity.
- Loss of LPL impaired macrophage elongation in response to chemotactic cues.
- Macrophages lacking LPL exhibited reduced transmigration capacity and decreased monocyte infiltration into the peritoneum.
Conclusions:
- L-plastin (LPL) plays a critical role in stabilizing long-lived podosomes within macrophages.
- LPL is essential for enabling macrophage motility, including elongation and transmigration.
- These findings highlight LPL as a key regulator of macrophage function in inflammatory and immune responses.
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