L-Plastin promotes podosome longevity and supports macrophage motility.
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.
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Julie Y
JY
Zhou
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Taylor P
TP
Szasz
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Phillip J
PJ
Stewart-Hutchinson
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Janardan
J
Sivapalan
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Elizabeth M
EM
Todd
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Lauren E
LE
Deady
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, United States.
John A
JA
Cooper
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Michael D
MD
Onken
Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, 63110, United States; Department of Pathology and Immunology, Division of Immunobiology, Washington University School of Medicine, St. Louis, MO, 63110, United States. Electronic address: morley_c@kids.wustl.edu.
S Celeste
SC
Morley
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000378:metabolism*; D000069261:Podosomes / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C066559:Lcp1 protein, mouse
Actin cytoskeleton; Cell motility; Macrophages; Podosomes; l-plastin