Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium
Cells use phagocytosis and macropinocytosis to internalise bulk material, which in phagotrophic organisms supplies the nutrients necessary for growth. Wildtype Dictyostelium amoebae feed on bacteria, but for decades laboratory work has relied on axenic mutants that can also grow on liquid media. We...
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doaj-058fdb0aa1d442d0ba8ebb5bfce966792021-05-04T23:43:10ZengeLife Sciences Publications LtdeLife2050-084X2015-03-01410.7554/eLife.04940Neurofibromin controls macropinocytosis and phagocytosis in DictyosteliumGareth Bloomfield0David Traynor1Sophia P Sander2Douwe M Veltman3Justin A Pachebat4Robert R Kay5MRC Laboratory of Molecular Biology, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Cambridge, United Kingdom; Centre for Human Development, Stem Cells and Regeneration, University of Southampton, Southampton, United KingdomMRC Laboratory of Molecular Biology, Cambridge, United KingdomDepartment of Plant Sciences, University of Cambridge, Cambridge, United Kingdom; Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, United KingdomMRC Laboratory of Molecular Biology, Cambridge, United KingdomCells use phagocytosis and macropinocytosis to internalise bulk material, which in phagotrophic organisms supplies the nutrients necessary for growth. Wildtype Dictyostelium amoebae feed on bacteria, but for decades laboratory work has relied on axenic mutants that can also grow on liquid media. We used forward genetics to identify the causative gene underlying this phenotype. This gene encodes the RasGAP Neurofibromin (NF1). Loss of NF1 enables axenic growth by increasing fluid uptake. Mutants form outsized macropinosomes which are promoted by greater Ras and PI3K activity at sites of endocytosis. Relatedly, NF1 mutants can ingest larger-than-normal particles using phagocytosis. An NF1 reporter is recruited to nascent macropinosomes, suggesting that NF1 limits their size by locally inhibiting Ras signalling. Our results link NF1 with macropinocytosis and phagocytosis for the first time, and we propose that NF1 evolved in early phagotrophs to spatially modulate Ras activity, thereby constraining and shaping their feeding structures.https://elifesciences.org/articles/04940amoebagrowthmacropinocytosisphagocytosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gareth Bloomfield David Traynor Sophia P Sander Douwe M Veltman Justin A Pachebat Robert R Kay |
spellingShingle |
Gareth Bloomfield David Traynor Sophia P Sander Douwe M Veltman Justin A Pachebat Robert R Kay Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium eLife amoeba growth macropinocytosis phagocytosis |
author_facet |
Gareth Bloomfield David Traynor Sophia P Sander Douwe M Veltman Justin A Pachebat Robert R Kay |
author_sort |
Gareth Bloomfield |
title |
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium |
title_short |
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium |
title_full |
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium |
title_fullStr |
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium |
title_full_unstemmed |
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium |
title_sort |
neurofibromin controls macropinocytosis and phagocytosis in dictyostelium |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2015-03-01 |
description |
Cells use phagocytosis and macropinocytosis to internalise bulk material, which in phagotrophic organisms supplies the nutrients necessary for growth. Wildtype Dictyostelium amoebae feed on bacteria, but for decades laboratory work has relied on axenic mutants that can also grow on liquid media. We used forward genetics to identify the causative gene underlying this phenotype. This gene encodes the RasGAP Neurofibromin (NF1). Loss of NF1 enables axenic growth by increasing fluid uptake. Mutants form outsized macropinosomes which are promoted by greater Ras and PI3K activity at sites of endocytosis. Relatedly, NF1 mutants can ingest larger-than-normal particles using phagocytosis. An NF1 reporter is recruited to nascent macropinosomes, suggesting that NF1 limits their size by locally inhibiting Ras signalling. Our results link NF1 with macropinocytosis and phagocytosis for the first time, and we propose that NF1 evolved in early phagotrophs to spatially modulate Ras activity, thereby constraining and shaping their feeding structures. |
topic |
amoeba growth macropinocytosis phagocytosis |
url |
https://elifesciences.org/articles/04940 |
work_keys_str_mv |
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1721476821234483200 |