L-Plastin promotes podosome longevity and supports macrophage motility

• Published in: Molecular immunology Vol. 78; pp. 79 - 88
• Main Authors: Zhou, Julie Y., Szasz, Taylor P., Stewart-Hutchinson, Phillip J., Sivapalan, Janardan, Todd, Elizabeth M., Deady, Lauren E., Cooper, John A., Onken, Michael D., Morley, S. Celeste
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2016
• Subjects: Actin cytoskeleton; Animals; Cell motility; Cell Movement - physiology; Cytoskeletal Proteins; l-plastin; Macrophages; Macrophages, Peritoneal - metabolism; Mice; Mice, Knockout; Microfilament Proteins; Microscopy, Confocal; Phosphoproteins - metabolism; Podosomes; Podosomes - metabolism; Cell motility; D10; Podosomes; APC; LPL; Actin cytoskeleton; Macrophages; l-plastin
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2016.08.012

•Podosome duration is reduced in the absence of l-plastin.•Resident peritoneal macrophages from l-plastin−/− mice do not polarize.•Efficient migration of resident peritoneal macrophages requires l-plastin. 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.