Cell polarity | EPFL Graph Search

Cell polarity refers to spatial differences in shape, structure, and function within a cell. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity, neurons in which signals propagate in one direction from dendrites to axons, and migrating cells. Furthermore, cell polarity is important during many types of asymmetric cell division to set up functional asymmetries between daughter cells. Many of the key molecular players implicated in cell polarity are well conserved. For example, in metazoan cells, the PAR-3/PAR-6/aPKC complex plays a fundamental role in cell polarity. While the biochemical details may vary, some of the core principles such as negative and/or positive feedback between different molecules are common and essential to many known polarity systems. Examples of polarized cells Epithelial cells

Characterization of RGS-7 as a regulator of forces involved in C. elegans early cell divisions

Simon Germann

Proper regulation of cell division is crucial to most organisms. Asymmetric division and unequal cleavage are one of the many mechanisms by which spatial regulation of cell division might be achieved. Indeed, by varying its polarity cues or by modulating the size of its daughters, a cell can potentially influence its cellular neighborhood and possibly act upon it. In C. elegans, asymmetric cell division occurs at early stages of development, and is induced by an asymmetric positioning of the spindle during mitosis. RGS-7, a member of the RGS protein family, is a potential candidate as a regulator of this process, and was shown to affect the balance of pulling forces responsible for the asymmetric position of the spindle, possibly acting through Gα and/or Gβ, which are heterotrimeric G-protein complex subunits involved in force generation in C. elegans early cell divisions. However, many aspects of the role this protein may have in this process remain to be elucidated. Using available rgs-7 mutants, RNA interference, spindle severing experiments and immunofluorescence assays, this study highlights the potential functions RGS-7 may provide to a dividing C. elegans embryo

2008

Identification of genetic interactors of ypa2 in Schizosaccharomyces pombe

Manuela Moraru

In this study, the fission yeast Schizosaccharomyces pombe was used as a model system to study the cellular signaling that underlies cell cycle progression. Phosphorylation plays an important part in the regulation of this process. Kinases catalyze the transfer of a phosphate group to a substrate, which may regulate its activity. Protein phosphatases oppose the activity of protein kinases; the balance of their activities regulates signaling flux in many signaling pathways. The Septation Initiation Network (SIN) is a signaling cascade that regulates cytokinesis in fission yeast. SIN signaling is triggered by a GTPase and is transduced by three protein kinases; phosphorylation plays an important role in controlling SIN signalling. Numerous genetic screens and biochemical analyses have identified phosphatases and kinases that regulate the SIN. The protein phosphatases Calcineurin/Protein Phosphatase 2B (PP2B) and Flp1p promote SIN signaling, while PP2A is a SIN inhibitor. PP2A is conserved and is activated by the chaperone Phosphatase Two A Phosphatase Activator (PTPA). S. pombe has two PTPA-related genes, ypa1 and ypa2; the deletion mutant of the latter rescues SIN mutants which cannot undergo cytokinesis, consistent with PP2A opposing SIN signaling. The phenotype of the deletion mutant of ypa2, indicates that it is involved in the control of cell polarity, cell growth, mitotic commitment and cytokinesis. In this study, we characterized the hypomorphic allele ypa2-S2 which rescues SIN mutants, but is otherwise largely normal. ypa2-s2 was used as bait in a synthetic genetic array screen, to identify genes whose products compensate for reduced function of Ypa2p. A large number of hits were identified, of which approximately ninety percent are novel genetic interactors of ypa2. Validation studies indicated that eighty percent of the interactions seen in the high-throughput screen can be reconstructed. The identified genes regulate several biological processes, including signal transduction and protein phosphorylation. This prompted us to further characterize the roles of Ckb1p and Flp1p, in regulating cytokinesis signaling. Ckb1p is a regulatory subunit for Casein Kinase II (CK II), which was previously implicated in polar growth. The phenotype of the mutant ypa2-S2 ckb1-â indicates that Ckb1p, similar to Ypa2p, contributes to the regulation of mitotic commitment and cytokinesis signaling. Furthermore, ckb1-â showed negative genetic interaction with PP2A and SIN mutants. Flp1p is a protein phosphatase that was reported to regulate mitotic commitment and to promote SIN signaling. The double mutant between ypa2-S2 and flp1-â showed cell separation defects and phenotypic analysis of double mutants between flp1-â and PP2A mutants indicates that these phosphatases cooperate in cell separation. Overall, this work has uncovered novel facets of the regulation of cytokinesis in S. pombe, implicating CK II in controlling SIN signaling, and uncovering cooperative interactions between different phosphatases in controlling cytokinesis.

EPFL2016

Analysis and Modeling of the Dynamics of Traction Forces during Cell Polarization and their Role in the Organization of Edge Activity

Zeno Messi

The capacity to break symmetry and organize activity to move directionally is a fundamental property of eukaryotic cells. To explain the organization of cell-edge activity, models commonly rely on front-to-back gradients of functional components or regulatory factors, but they do not explain how the front-back axis is defined in the first place. Recently, a novel and successful principle for self-organization of cell-edge activity was proposed, in which local cell-edge dynamics depends on the distance from the cell center, but not on the orientation with respect to the front-back axis. In this thesis, we test the hypothesis that edge motion is controlled by distance sensing via traction forces.\par We show that traction forces exerted on the substrate by polarizing cells are highly dynamical and follow motion of the cell-edge, that stress increases with the distance from the cell center and that maximal forces are located at a fixed distance from the edge near the sites of protrusion-retraction switches. We observe that traction forces correlate with edge extension in cell populations under different experimental conditions. We demonstrate with a fully mechanical model that distance dependence of the force is an emergent property of elastic fiber networks. We next show that dynamics of traction forces and cell-edge motion are correlated during protrusion-retraction cycles, indicating that traction forces trigger the switch from protrusion to retraction. Actin retrograde flow correlates with stress during retraction but not during protrusion suggesting that increase of stress during protrusion is independent of the motion of the actin network. Finally, incorporating a mechanism of cytoskeletal turnover in our model of fiber network we produce systems that display oscillatory fluctuations of their edge and other experimental behaviors.\par Our results provide strong evidence that traction forces play a major role in the organization of cell-edge activity and polarization.

EPFL2021