AUTHOR=Bodinier Romain , Sabra Ayman , Leiba Jade , Marchetti Anna , Lamrabet Otmane , Ayadi Imen , Filić Vedrana , Kawata Takefumi , Weber Igor , Cosson Pierre 

TITLE=Role of LrrkA in the Control of Phagocytosis and Cell Motility in Dictyostelium discoideum

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.629200

DOI=10.3389/fcell.2021.629200

ISSN=2296-634X

ABSTRACT=<p>LrrkA is a <italic>Dictyostelium discoideum</italic> kinase with leucine-rich repeats. LrrkA stimulates Kil2 and intra-phagosomal killing of ingested bacteria in response to folate. In this study, we show that genetic inactivation of <italic>lrrkA</italic> also causes a previously unnoticed phenotype: <italic>lrrkA</italic> KO cells exhibit enhanced phagocytosis and cell motility compared to parental cells. This phenotype is cell autonomous, is reversible upon re-expression of LrrkA, and is not due to an abnormal response to inhibitory quorum-sensing factors secreted by <italic>D. discoideum</italic> in its medium. In addition, folate increases motility in parental <italic>D. discoideum</italic> cells, but not in <italic>lrrkA</italic> KO cells, suggesting that LrrkA plays a pivotal role in the cellular response to folate. On the contrary, <italic>lrrkA</italic> KO cells regulate gene transcription in response to folate in a manner indistinguishable from parental cells. Overall, based on analysis of mutant phenotypes, we identify gene products that participate in the control of intracellular killing, cell motility, and gene transcription in response to folate. These observations reveal a mechanism by which <italic>D. discoideum</italic> encountering bacterially-secreted folate can migrate, engulf, and kill bacteria more efficiently.</p>