title: Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation.
abstract: Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C alpha. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.
authors.affiliation: Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. marle@imk.liu.se
authors.forename: M
authors.initials: M
authors.lastname: Lerm
authors.forename: A
authors.initials: A
authors.lastname: Holm
authors.forename: A
authors.initials: A
authors.lastname: Seiron
authors.forename: E
authors.initials: E
authors.lastname: Särndahl
authors.forename: K-E
authors.initials: KE
authors.lastname: Magnusson
authors.forename: B
authors.initials: B
authors.lastname: Rasmusson
mesh_terms: D000199:Actins / Q000032:analysis / Q000502:physiology; D000818:Animals; D002460:Cell Line; D006028:Glycosphingolipids / Q000502:physiology; D007893:Leishmania donovani / Q000502:physiology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D051379:Mice; D010588:Phagosomes / Q000502:physiology*; D051571:Protein Kinase C-alpha / Q000502:physiology; D021381:Protein Transport; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: D000199:Actins; D006028:Glycosphingolipids; D052118:Lysosomal-Associated Membrane Protein 1; C008290:lipophosphonoglycan; D051571:Protein Kinase C-alpha; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein