LrrKa, a kinase with leucine-rich repeats links folate sensing with Kil2 activity and intracellular killing

Bodinier, Romain; Leiba, Jade; Sabra, Ayman; Jauslin, Tania; Lamrabet, Otmane; Guilhen, Cyril; Marchetti, Anna; Iwade, Yumi; Kawata, Takefumi; Du Fresne Von Hohenesche, Wanessa Cristina; Cosson, Pierre

doi:10.1111/cmi.13129

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Title		LrrKa, a kinase with leucine-rich repeats links folate sensing with Kil2 activity and intracellular killing
Authors		Bodinier, Romain Leiba, Jade Sabra, Ayman Jauslin, Tania Lamrabet, Otmane Guilhen, Cyril Marchetti, Anna Iwade, Yumi Kawata, Takefumi Du Fresne Von Hohenesche, Wanessa Cristina Cosson, Pierre show all authors [1 - 11]
Published in		Cellular Microbiology. 2019, 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.
Identifiers		DOI: 10.1111/cmi.13129 PMID: 31652367
Full text		Article (Published version) (10.4 MB) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research group		Phagocytose (140)
Project		Swiss National Science Foundation: 31003A_172951
Citation (ISO format)		BODINIER, Romain et al. LrrKa, a kinase with leucine-rich repeats links folate sensing with Kil2 activity and intracellular killing. In: Cellular Microbiology, 2019, p. e13129. doi: 10.1111/cmi.13129 https://archive-ouverte.unige.ch/unige:126166