Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum

Abstract

Chemotaxis is the ability of cells to move in the direction of an external gradient of signaling molecules. Cells are guided by actin-filled protrusions in the front, whereas myosin filaments retract the rear of the cell. Previous work demonstrated that chemotaxis of unpolarized amoeboid Dictyostelium discoideum cells is mediated by two parallel pathways, phosphoinositide-3-kinase (PI3K) and phospholipase A2 (PLA2). Here, we show that polarized cells exhibit very good chemotaxis with inhibited PI3K and PLA2 activity. Using genetic screens, we demonstrate that this activity is mediated by a soluble guanylyl cyclase, providing two signals. The protein localizes to the leading edge where it interacts with actin filaments, whereas the cyclic guanosine monophosphate product induces myosin filaments in the rear of the cell. We conclude that chemotaxis is mediated by multiple signaling pathways regulating protrusions at the front and rear of the cell. Cells that express only rear activity are polarized but do not exhibit chemotaxis, whereas cells with only front signaling are unpolarized but undergo chemotaxis.

Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling

“…3). Although sGC⌬Cat does not produce cGMP, it can mediate the front signal for chemotaxis (18,33). On the contrary, sGC⌬N shows WT-like cGMP production and can mediate the rear signals for chemotaxis (18,33).…”

“…sGC contains an N-terminal domain, which shows no homology to any other known protein sequence, and a catalytic domain that have distinct functions during chemotaxis (18,33). In chemotaxis, the N-terminal domain mediates the ''front'' signal via interaction with the actin cytoskeleton at the leading-edge pseudopod, whereas the catalytic domain mediates the ''rear'' signal via cGMP-dependent myosin activation at the tail (18,33). To examine whether both domains of sGC have some functional differences in electrotaxis, we further studied gc-null cells expressing either sGC with an inactivated catalytic domain (sGC⌬Cat) or sGC with a deleted N-terminal domain (sGC⌬N) (Fig.…”

“…Dictyostelium cells present a well-established model for elucidating the mechanisms and regulation of amoeboid movements (13)(14)(15)(16)(17). Their chemotactic responses have been extensively studied at the molecular and cellular levels, which has resulted in the identification of multiple and parallel chemotactic signaling pathways (18)(19)(20)(21). Because Dictyostelium cells exhibit strong electrotaxis, they are also useful for studying the mechanism of this process (22,23).…”

High Resolution Tracking of Cell Membrane Dynamics in Moving Cells: an Electrifying Approach

“…Cell motility can be regulated by both internal and external signals that activate intricate signalling cascades resulting in highly dynamic, localised and coordinated remodelling of components of the actin cytoskeleton [1,38,21,29,28]. To further elucidate the regulation of cytoskeleton dynamics we must not only identify the structural and regulatory components involved, but critically quantify their spatial-temporal dynamics during movement and their correlation to one another.…”

“…For example, Dalous et al [9] used QuimP to study actin and myo-II relocalization in Dictyostelium discoideum, a unicellular amoeba that plays an important role as a model organism for cell motility [17,25]. QuimP also outputs numerous statistics useful for analysis including node positions, measured intensities, area changes, cell speed, convexity and centre of mass, as well as computed averages [38].…”