title: Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium.
abstract: 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.
authors: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: Gareth
authors: G
authors: Bloomfield
authors: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: David
authors: D
authors: Traynor
authors: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: Sophia P
authors: SP
authors: Sander
authors: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: Douwe M
authors: DM
authors: Veltman
authors: Department of Plant Sciences, University of Cambridge, Cambridge, United Kingdom.
authors: Justin A
authors: JA
authors: Pachebat
authors: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: Robert R
authors: RR
authors: Kay
mesh_terms: D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics; D009154:Mutation; D025542:Neurofibromin 1 / Q000235:genetics* / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics*; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010873:Pinocytosis / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism
chemical_list: D025542:Neurofibromin 1; D015800:Protozoan Proteins; D019869:Phosphatidylinositol 3-Kinases; D018631:ras Proteins
keywords: amoeba; cell biology; dictyostelium; evolutionary biology; genomics; growth; macropinocytosis; phagocytosis