A G-protein-coupled chemoattractant receptor recognizes lipopolysaccharide for bacterial phagocytosis.
A G-protein-coupled chemoattractant receptor recognizes lipopolysaccharide for bacterial phagocytosis.
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DOI：
10.1371/journal.pbio.2005754
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发表时间：
2018-05
期刊：
影响因子：
9.8
通讯作者：
Jin T
中科院分区：
文献类型：
--
作者：
Pan M;Neilson MP;Grunfeld AM;Cruz P;Wen X;Insall RH;Jin T
Phagocytes locate microorganisms via chemotaxis and then consume them using phagocytosis. Dictyostelium amoebas are stereotypical phagocytes that prey on diverse bacteria using both processes. However, as typical phagocytic receptors, such as complement receptors or Fcγ receptors, have not been found in Dictyostelium, it remains mysterious how these cells recognize bacteria. Here, we show that a single G-protein-coupled receptor (GPCR), folic acid receptor 1 (fAR1), simultaneously recognizes the chemoattractant folate and the phagocytic cue lipopolysaccharide (LPS), a major component of bacterial surfaces. Cells lacking fAR1 or its cognate G-proteins are defective in chemotaxis toward folate and phagocytosis of Klebsiella aerogenes. Computational simulations combined with experiments show that responses associated with chemotaxis can also promote engulfment of particles coated with chemoattractants. Finally, the extracellular Venus-Flytrap (VFT) domain of fAR1 acts as the binding site for both folate and LPS. Thus, fAR1 represents a new member of the pattern recognition receptors (PRRs) and mediates signaling from both bacterial surfaces and diffusible chemoattractants to reorganize actin for chemotaxis and phagocytosis. How eukaryotic cells find and interact with bacteria is a fundamental question in biology. Eukaryotic phagocytes are cells that engulf and digest bacteria. These include single-celled organisms, such as amoeba, and cell types of multicellular organisms, such as macrophages. The current dogma is that phagocytic cells use at least two types of receptors for defense against invading pathogens: one for detecting and chasing pathogens via chemotaxis and another one for recognizing and eliminating them via phagocytosis. Detection and chasing is facilitated by G-protein-coupled receptors (GPCRs), whereas recognition and elimination employ pattern recognition receptors (PRRs). However, the social amoeba Dictyostelium discoideum does not encode orthologs of any known PRRs or phagocytic receptors; yet they are highly evolved as professional phagocytes that chase bacteria via chemotaxis and consume them as food through phagocytosis. Here, we show that this stereotypical phagocyte utilizes folic acid receptor 1 (fAR1), a class C GPCR, to simultaneously detect bacterial secreted folate for chasing bacteria and microbial-associated molecular patterns (MAMPs)—lipopolysaccharide (LPS)—for engulfing and consuming them.
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影响因子：
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作者：
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发表时间：
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