Role of protein kinase C alpha for uptake of unopsonized prey and phagosomal maturation in macrophages.
Protein kinase C alpha (PKC alpha) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the disassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKC alpha. To investigate a possible connection between PKC alpha and LPG's effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PCK alpha (DN PKC alpha). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKC alpha-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKC alpha is involved in F-actin turnover in macrophages and that PKC alpha-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKC alpha by LPG.
Holm
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A
Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden. asa.holm@imk.lu.se
Tejle
K
K
Gunnarsson
T
T
Magnusson
K-E
KE
Descoteaux
A
A
Rasmusson
B
B
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D006028:Glycosphingolipids / Q000378:metabolism*; D007893:Leishmania donovani / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D006028:Glycosphingolipids; D051907:Lysosomal Membrane Proteins; D009895:Opsonin Proteins; C008290:lipophosphonoglycan; D011493:Protein Kinase C