Cell motility mediates tissue size regulation in Dictyostelium

Abstract

Little is known about how organisms regulate the size of multicellular structures. This review condenses some of the observations about how Dictyostelium regulates the size of fruiting bodies. Very large fruiting bodies tend to fall over, and one of the ways Dictyostelium cells prevent this is by breaking up the aggregation streams when there is an excessive number of cells in the stream. Developing cells simultaneously secrete and sense counting factor (CF), a 450 kDa complex of proteins. Diffusion calculations showed that as the number of cells in a stream or group increases, the local concentration of CF will increase, allowing the cells to sense the number of cells in the stream or group. Computer simulations predicted that a high level of CF could trigger stream breakup by decreasing cell-cell adhesion and/or increasing cell motility, effectively causing the stream to dissipate and begin to fall apart. The prediction that adhesion and motility affect group size is supported by observations that decreasing adhesion by adding antibodies that bind to adhesion protein causes the formation of smaller groups, while increasing adhesion by overexpressing adhesion proteins, or decreasing motility with drugs that disrupt actin function both cause the formation of larger groups. CF both decreases adhesion and increases motility. CF increases motility in part by increasing actin polymerization and myosin phosphorylation, and decreasing myosin polymerization. New observations using a fusion of a green fluorescent protein to a protein fragment that binds polymerized actin show that in live cells CF does not affect the distribution of polymerized actin. CF increases the levels of ABP-120, an actin-bundling protein, and new observations indicate that very low levels of CF cause an increase in levels of myoB, an unconventional myosin. Our current understanding of group size regulation in Dictyostelium is thus that motility plays a key role, and that to regulate group size cells regulate the expression of at least two proteins, as well as regulating the polymerization of both actin and myosin.