Abstract
The mechanism of chemotaxis is one of the most interesting issues in modern cell biology. Recent work shows that shallow chemoattractant gradients do not induce the generation of pseudopods, as has been predicted in many models. This poses the question of how else cells can steer towards chemoattractants. Here we use a new computational algorithm to analyze the extension of pseudopods by Dictyostelium cells. We show that a shallow gradient of cAMP induces a small bias in the direction of pseudopod extension, without significantly affecting parameters such as pseudopod frequency or size. Persistent movement, caused by alternating left/right splitting of existing pseudopodia, amplifies the effects of this bias by up to 5-fold. Known players in chemotactic pathways play contrasting parts in this mechanism; PLA2 and cGMP signal to the cytoskeleton to regulate the splitting process, while PI 3-kinase and soluble guanylyl cyclase mediate the directional bias. The coordinated regulation of pseudopod generation, orientation and persistence by multiple signaling pathways allows eukaryotic cells to detect extremely shallow gradients.
Highlights
Chemotaxis plays essential roles in development, metastasis and finding bacteria during infection [1,2,3]
The gradient induces a strong bias of the position where pseudopodia emerge, such that pseudopodia appear more likely at the side of the cell closer towards the gradient than at other sides of the cell (Fig. 1C)
Many eukaryotic cells extend pseudopodia. It appears that the movement of Dictyostelium cells in a chemotactic gradient is firmly based on the ordered extension of pseudopodia in the absence of external cues [16] (Figure 7)
Summary
Chemotaxis plays essential roles in development, metastasis and finding bacteria during infection [1,2,3]. By increasing the persistence time, cells disperse better during food seeking [9], move longer distances during morphogenesis [10,11] and may escape into the environment during metastasis [12,13]. Chemotaxis may represent another field of cell biology where persistence could be critical, because cells moving without persistence need a chemotaxis bias for each new pseudopod, while cells moving persistently will accumulate directional accuracy at each subsequent pseudopod
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