Dowdell, A., Paschke, P. I., Thomason, P. A., Tweedy, L. and Insall, R. H. (2023) Competition between chemoattractants causes unexpected complexity and can explain negative chemotaxis. Current Biology, 32(9), 1704-1715.e3. (doi: 10.1016/j.cub.2023.03.006) (PMID:37001521)
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Abstract
Negative chemotaxis, where eukaryotic cells migrate away from repellents, is important throughout biology, for example, in nervous system patterning and resolution of inflammation. However, the mechanisms by which molecules repel migrating cells are unknown. Here, we use predictive modeling and experiments with Dictyostelium cells to show that competition between different ligands that bind to the same receptor leads to effective chemorepulsion. 8-CPT-cAMP, widely described as a simple chemorepellent, is inactive on its own and only repels cells when it acts in combination with the attractant cAMP. If cells degrade either competing ligand, the pattern of migration becomes more complex; cells may be repelled in one part of a gradient but attracted elsewhere, leading to populations moving in different directions in the same assay or converging in an arbitrary place. More counterintuitively still, two chemicals that normally attract cells can become repellent when combined. Computational models of chemotaxis are now accurate enough to predict phenomena that have not been anticipated by experiments. We have used them to identify new mechanisms that drive reverse chemotaxis, which we have confirmed through experiments with real cells. These findings are important whenever multiple ligands compete for the same receptors.
Item Type: | Articles |
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Additional Information: | The authors are grateful to Cancer Research UK (CRUK) for core funding to the CRUK Beatson Institute (A31287) and to R.H.I. (A19257), and to the Wellcome Trust for grant 221786/Z/20/Z to R.H.I. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Tweedy, Dr Luke and Insall, Professor Robert and Thomason, Dr Peter and Dowdell, Adam and Paschke, Dr Peggy |
Authors: | Dowdell, A., Paschke, P. I., Thomason, P. A., Tweedy, L., and Insall, R. H. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Current Biology |
Publisher: | Elsevier (Cell Press) |
ISSN: | 0960-9822 |
ISSN (Online): | 1879-0445 |
Published Online: | 30 March 2023 |
Copyright Holders: | Copyright © 2023 The Authors |
First Published: | First published in Current Biology 33(9): 1704-1715.e3 |
Publisher Policy: | Reproduced under a Creative Commons License |
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