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Bloomfield, Gareth, Traynor, David, Sander, SP Sophia P, Veltman, DM Douwe M, Pachebat, JA Justin A, Kay, RR Robert R, (2015) ' Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium. ' Elife 4
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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.
Status: epublish Type: Journal article Source: PUBMED PubMed ID: 25815683

Genes addressed in this paper
DDB_G0279751 DDB_G0279753 axeB
Topics in this paper
Protein Physical Properties X X X

Cellular Location


Signal Transduction


Phylogenetic Analysis

DNA/RNA Sequence Features X X X