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Bodinier, Romain, Leiba, Jade, Sabra, Ayman, Jauslin, TN Tania N, Lamrabet, Otmane, Guilhen, Cyril, Marchetti, Anna, Iwade, Yumi, Kawata, Takefumi, Lima, WC Wanessa C, Cosson, Pierre, (2019) ' LrrkA, a kinase with Leucine-Rich Repeats links folate sensing with Kil2 activity and intracellular killing. ' Cell. Microbiol. e13129

 

Abstract:Phagocytic cells ingest bacteria by phagocytosis and kill them efficiently inside phagolysosomes. The molecular mechanisms involved in intracellular killing and their regulation are complex and still incompletely understood. Dictyostelium discoideum has been used as a model to discover and to study new gene products involved in intracellular killing of ingested bacteria. In this study, we performed random mutagenesis of Dictyostelium cells, and isolated a mutant defective for growth on bacteria. This mutant is characterized by the genetic inactivation of the lrrkA gene, which encodes a protein with a kinase domain and leucine-rich repeats. LrrkA knockout (KO) cells kill ingested K. pneumoniae bacteria inefficiently. This defect is not additive to the killing defect observed in kil2 KO cells, suggesting that the function of Kil2 is partially controlled by LrrkA. Indeed, lrrkA KO cells exhibit a phenotype similar to that of kil2 KO cells: intraphagosomal proteolysis is inefficient and both intraphagosomal killing and proteolysis are restored upon exogenous supplementation with magnesium ions. Bacterially secreted folate stimulates intracellular killing in Dictyostelium cells, but this stimulation is lost in cells with genetic inactivation of kil2, lrrkA or far1. Together these results indicate that the stimulation of intracellular killing by folate involves Far1 (the cell surface receptor for folate), LrrkA and Kil2. This study is the first identification of a signaling pathway regulating intraphagosomal bacterial killing in Dictyostelium cells.
Status:	aheadofprint	Type:	Journal article	Source:	PUBMED	PubMed ID:	31652367

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	Genes addressed in this paper
	DDB_G0278909	drkA	drkB	drkC	drkD	far1	kil1	kil2
Topics in this paper
Mammalian Gene Related					X
Protein Functional Domain	X	X	X	X	X
Strains/Constructs					X		X	X
Non-mammalian Gene Related					X
Synonym
Function/Process					X		X	X
Signal Transduction					X	X	X	X
Genetic Interactions					X		X	X
Mutants/Phenotypes					X	X	X	X
Growth					X

	Genes addressed in this paper
	lrrkB	qkgA-1	qkgA-2	vps13F
Topics in this paper
Mammalian Gene Related
Protein Functional Domain	X	X	X
Strains/Constructs
Non-mammalian Gene Related
Synonym	X
Function/Process				X
Signal Transduction
Genetic Interactions
Mutants/Phenotypes				X
Growth