Navigation of Chemotactic Cells by Parallel Signaling to Pseudopod Persistence and Orientation

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

Food Searching Strategy of Amoeboid Cells by Starvation Induced Run Length Extension

Food searching strategies of animals are key to their success in heterogeneous environments. The optimal search strategy may include specialized random walks such as Levy walks with heavy power-law tail distributions, or persistent walks with preferred movement in a similar direction. We have investigated the movement of the soil amoebae Dictyostelium searching for food. Dictyostelium cells move by extending pseudopodia, either in the direction of the previous pseudopod (persistent step) or in a different direction (turn). The analysis of ∼4000 pseudopodia reveals that step and turn pseudopodia are drawn from a probability distribution that is determined by cGMP/PLA2 signaling pathways. Starvation activates these pathways thereby suppressing turns and inducing steps. As a consequence, starved cells make very long nearly straight runs and disperse over ∼30-fold larger areas, without extending more or larger pseudopodia than vegetative cells. This ‘win-stay/lose-shift’ strategy for food searching is called Starvation Induced Run-length Extension. The SIRE walk explains very well the observed differences in search behavior between fed and starving organisms such as bumble-bees, flower bug, hoverfly and zooplankton

The Ordered Extension of Pseudopodia by Amoeboid Cells in the Absence of External Cues

Eukaryotic cells extend pseudopodia for movement. In the absence of external cues, cells move in random directions, but with a strong element of persistence that keeps them moving in the same direction Persistence allows cells to disperse over larger areas and is instrumental to enter new environments where spatial cues can lead the cell. Here we explore cell movement by analyzing the direction, size and timing of ∼2000 pseudopodia that are extended by Dictyostelium cells. The results show that pseudpopod are extended perpendicular to the surface curvature at the place where they emerge. The location of new pseudopods is not random but highly ordered. Two types of pseudopodia may be formed: frequent splitting of an existing pseudopod, or the occasional extension of a de novo pseudopod at regions devoid of recent pseudopod activity. Split-pseudopodia are extended at ∼60 degrees relative to the previous pseudopod, mostly as alternating Right/Left/Right steps leading to relatively straight zigzag runs. De novo pseudopodia are extended in nearly random directions thereby interrupting the zigzag runs. Persistence of cell movement is based on the ratio of split versus de novo pseudopodia. We identify PLA2 and cGMP signaling pathways that modulate this ratio of splitting and de novo pseudopodia, and thereby regulate the dispersal of cells. The observed ordered extension of pseudopodia in the absence of external cues provides a fundamental insight into the coordinated movement of cells, and might form the basis for movement that is directed by internal or external cues

Roc, a Ras/GTPase domain in complex proteins

We identified a novel group of the Ras/GTPase superfamily, termed Roc, that is present as domain in complex proteins together with other domains, including leucine-rich repeats (LRRs), ankyrin repeats, WD40 repeats, kinase domains, RasGEF and RhoGAP domains. Roc is always succeeded by a novel 300–400-amino-acid-long domain, termed COR. Proteins with Roc/COR are present in prokaryotes, Dictyostelium, plants and metazoa.

Quimp3, an automated pseudopod-tracking algorithm

To understand movement of amoeboid cells we have developed an information tool that automatically detects protrusions of moving cells. The algorithm uses digitized cell recordings at a speed of ∼1 image per second that are analyzed in three steps. In the first part, the outline of a cell is defined as a polygon of ∼150 nodes, using the previously published Quimp2 program. By comparing the position of the nodes in place and time, each node contains information on position, local curvature and speed of movement. The second part uses rules for curvature and movement to define the position and time of start and end of a growing pseudopod. This part of the algorithm produces quantitative data on size, surface area, lifetime, frequency and direction of pseudopod extension. The third part of the algorithm assigns qualitative properties to each pseudopod. It decides on the origin of a pseudopod as splitting of an existing pseudopod or as extension de novo. It also decides on the fate of each pseudopod as merged with the cell body or retracted. Here we describe the pseudopod tool and present the first data based on the analysis of ∼1,000 pseudopodia extended by Dictyostelium cells in the absence of external cues

A model for cGMP signal transduction in Dictyostelium in perspective of 25 years of cGMP research

The chemoattactant mediated cGMP response of Dictyostelium cells was discovered about twenty-five years ago. Shortly thereafter, guanylyl cyclases, cGMP-phosphodiesterases and cGMP-binding proteins were detected already in lysates, but the encoding genes were discovered only very recently. The deduced proteins appear to be very different from proteins with the same function in metazoa. In this review we discuss these new findings in perspective of the previously obtained biochemical and functional data on cGMP in Dictyostelium.

Reasons for fear during childbirth – A population based study with women in the Gothenburg area

Bakgrund: En negativ förlossningsupplevelse kan resultera i sekundär förlossningsrädsla. Detta gör det viktigt att identifiera vilka faktorer som bidrar till rädsla under förlossningen. Detta är mycket lite utforskat. Syfte: Syftet var att kartlägga förekomst av och orsaker till rädsla under förlossningen hos kvinnor i Göteborgsområdet. Metod: Analys av en fråga ur en redan genomförd enkätstudie utfördes med kvalitativ innehållsanalys samt kvantifiering av förekomst, kategorier och underkategorier. Resultat: Nästan två tredjedelar av kvinnorna upplevde rädsla under förlossningen. Analysen resulterade i åtta kategorier som beskrev orsaker till rädsla under förlossningen. Kategorierna var; Smärta, Komplikationer under förlossningen, Egen förmåga, Förlossningsförlopp, Erfarenhet, Utsatt situation, Sjukhusmiljö och Fel på barnet. Konklusion: Det är samma faktorer som orsakar förlossningsrädsla under graviditet och rädsla under förlossningen. Därför är det viktigt att som barnmorska arbeta förebyggande, både inom mödrahälsovård och på förlossningen med hjälp av information och stöd