Bodinier Romain, Sabra Ayman, Leiba Jade, Marchetti Anna, Lamrabet Otmane, Ayadi Imen, Filić Vedrana, Kawata Takefumi, Weber Igor, Cosson Pierre
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Division of Molecular Biology, Ruder Boskovic Institute, Zagreb, Croatia.
Front Cell Dev Biol. 2021 Mar 8;9:629200. doi: 10.3389/fcell.2021.629200. eCollection 2021.
LrrkA is a 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 also causes a previously unnoticed phenotype: 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 in its medium. In addition, folate increases motility in parental cells, but not in KO cells, suggesting that LrrkA plays a pivotal role in the cellular response to folate. On the contrary, 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 encountering bacterially-secreted folate can migrate, engulf, and kill bacteria more efficiently.
LrrkA是一种具有富含亮氨酸重复序列的激酶。LrrkA刺激Kil2以及响应叶酸时对摄入细菌的吞噬体内杀伤作用。在本研究中，我们表明其基因失活还会导致一种先前未被注意到的表型：与亲本细胞相比，LrrkA基因敲除（KO）细胞表现出增强的吞噬作用和细胞运动性。这种表型是细胞自主性的，在LrrkA重新表达后是可逆的，并且不是由于对其培养基中分泌的抑制性群体感应因子的异常反应所致。此外，叶酸增加亲本细胞的运动性，但不增加LrrkA基因敲除细胞的运动性，这表明LrrkA在细胞对叶酸的反应中起关键作用。相反，LrrkA基因敲除细胞以与亲本细胞无法区分的方式响应叶酸调节基因转录。总体而言，基于对突变体表型的分析，我们鉴定出参与响应叶酸控制细胞内杀伤、细胞运动性和基因转录的基因产物。这些观察结果揭示了一种机制，通过该机制，遇到细菌分泌叶酸的细胞可以更有效地迁移、吞噬和杀死细菌。
