Living on soup: macropinocytic feeding in amoebae

Abstract

Macropinocytosis is used by a variety of amoebae for feeding on liquid medium. The amoebae project cups and ruffles from their plasma membrane, driven by actin polymerization, and eventually fuse these back to the membrane, entrapping droplets of medium into internal vesicles. These vesicles are of up to several microns in diameter and are processed through the lysosomal digestive system to extract nutrients. Recognizably the same process is used in metazoan cells for a number of medically important purposes, including the pathological growth of cancer cells. We describe the discovery of macropinocytosis in Dictyostelium amoebae, its genetic regulation by the NF1 RasGAP, and the tools available for its investigation. Work on Dictyostelium over the last 30 years has identified many genes that may be important for macropinocytosis, which are listed at dictyBase, and give a basis for mechanistic studies. We argue that the actin cytoskeleton is organized for macropinocytosis by a signalling patch of PIP3 and active Ras and Rac, together with their regulatory proteins and effectors, including the protein kinases Akt and SGK. The Scar/ WAVE complex is recruited to the periphery of this patch, triggering the formation of a hollow ring of protrusive actin polymerization, and eventually a macropinocytic cup. Major problems to be addressed include: the dynamics sustaining macropinocytic patches and the mechanism of Scar/WAVE recruitment; the mechanisms of cup closure and of membrane fusion; the ecological situations where amoebae feed by macropinocytosis; and the evolutionary relationship between macropinocytosis and growth factor signalling.

The endocytic pathways of Dictyostelium discoideum

“…Macropinosome formation is particularly interesting, as the cups are able to spontaneously self-organise in the absence of any spatial or physical signals from a particulate template. This is described elsewhere, including in this issue (Buckley and King, 2017;Kay et al, 2019;Williams et al, 2019). The focus of this review will instead be on the maturation pathway of these compartments in Dictyostelium from the moment the phagosomes and macropinosomes have formed, until their eventual resolution.…”

Phospholipids containing ether-bound hydrocarbon-chains are essential for efficient phagocytosis and neutral lipids of the ester-type perturb development in Dictyostelium

“…In particular this involves sphingolipids, the hydrolysis of phosphatidylcholine, and most of all, differential phosphorylation of the inositol head-group followed by local membrane recruitment of specific signalling proteins ( Divecha and Irvine, 1995 ). Ground-breaking work on the last topic was conducted in the field of Dictyostelium ( Parent et al, 1998 ; Iijima and Devreotes, 2002 ), although these lipid modifications were then shown to recruit cytoskeletal proteins to the sites of phagocytosis ( Dormann et al, 2004 ) and turned out to be especially important for macropinocytosis ( Hoeller et al, 2013 ; Kay et al, 2019 ; Vines and King, 2019 ) rather than chemotaxis ( Hoeller and Kay, 2007 ).…”

Micro-topographical guidance of macropinocytic signaling patches

“…From lack of their presence in the aggregation-stage NC4 cells, migratory roles of ventral patches in Dictyostelium is not clear. This puzzle parallels that for large-scale macropinocytosis in Dictyostelium as extracellular environment that supports it is so far unknown (Kay et al, 2019). We envisage that the natural habitat that supports efficient macropinocytosis; i.e.…”