Biochemical and Biophysical Research Communications, Vol.507, No.1-4, 304-310, 2018
Chemoattractant receptors activate, recruit and capture G proteins for wide range chemotaxis
The wide range sensing of extracellular signals is a common feature of various sensory cells. Eukaryotic chemotactic cells driven by GPCRs and their cognate G proteins are one example. This system endows the cells directional motility towards their destination over long distances. There are several mechanisms to achieve the long dynamic range, including negative regulation of the receptors upon ligand interaction and spatial regulation of G proteins, as we found recently. However, these mechanisms are insufficient to explain the 10(5)-fold range of chemotaxis seen in Dictyostelium. Here, we reveal that the receptor-mediated activation, recruitment, and capturing of G proteins mediate chemotactic signaling at the lower, middle and higher concentration ranges, respectively. These multiple mechanisms of G protein dynamics can successfully cover distinct ranges of ligand concentrations, resulting in seamless and broad chemotaxis. Furthermore, single-molecule imaging analysis showed that the activated Ga subunit forms an unconventional complex with the agonist-bound receptor. This complex formation of GPCR-G alpha increased the membrane-binding time of individual G alpha molecules and therefore resulted in the local accumulation of G alpha. Our findings provide an additional chemotactic dynamic range mechanism in which multiple G protein dynamics positively contribute to the production of gradient information. (C) 2018 The Authors. Published by Elsevier Inc.
Keywords:Eukaryotic chemotaxis;Gradient sensing;Dynamic range extension;G protein-coupled receptor;Single-molecule analysis