Showing papers by "Chris Janetopoulos published in 2013"
TL;DR: The spatiotemporal localization of cytoskeletal and signaling molecules and the FA-mediated responses in a number of signaling mutants are investigated to further the understanding of the core regulatory elements that are crucial for cell migration.
Abstract: Summary Dictyostelium discoideum shows chemotaxis towards folic acid (FA) throughout vegetative growth, and towards cAMP during development. We determined the spatiotemporal localization of cytoskeletal and signaling molecules and investigated the FA-mediated responses in a number of signaling mutants to further our understanding of the core regulatory elements that are crucial for cell migration. Proteins enriched in the pseudopods during chemotaxis also relocalize transiently to the plasma membrane during uniform FA stimulation. In contrast, proteins that are absent from the pseudopods during migration redistribute transiently from the PM to the cytosol when cells are globally stimulated with FA. These chemotactic responses to FA were also examined in cells lacking the GTPases Ras C and G. Although Ras and phosphoinositide 3-kinase activity were significantly decreased in Ras G and Ras C/G nulls, these mutants still migrated towards FA, indicating that other pathways must support FA-mediated chemotaxis. We also examined the spatial movements of PTEN in response to uniform FA and cAMP stimulation in phospholipase C (PLC) null cells. The lack of PLC strongly influences the localization of PTEN in response to FA, but not cAMP. In addition, we compared the gradient-sensing behavior of polarized cells migrating towards cAMP to that of unpolarized cells migrating towards FA. The majority of polarized cells make U-turns when the cAMP gradient is switched from the front of the cell to the rear. Conversely, unpolarized cells immediately extend pseudopods towards the new FA source. We also observed that plasma membrane phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5) P 3 ] levels oscillate in unpolarized cells treated with Latrunculin-A, whereas polarized cells had stable plasma membrane PtdIns(3,4,5) P 3 responses toward the chemoattractant gradient source. Results were similar for cells that were starved for 4 hours, with a mixture of polarized and unpolarized cells responding to cAMP. Taken together, these findings suggest that similar components control gradient sensing during FA- and cAMP-mediated motility, but the response of polarized cells is more stable, which ultimately helps maintain their directionality.
30 citations
TL;DR: This first systematic study of GABA metabolism in Dictyostelium discoideum is conducted by disrupting genes related to GABA metabolism and signaling and identified the GABAB receptor-like family member GrlB as the major GABA receptor during early development.
16 citations
01 Jan 2013
TL;DR: A review of the signaling mechanisms regulating directed migration and the role of polarity and development on the current understanding of this process highlights new findings and suggests that this chemical cue should be used when a developmental defect is suspected.
Abstract: Cells have an amazing ability to sense very shallow gradients of chemoattractants and move directionally. This fundamental process is critical for development and numerous disease states. Dictyostelium has emerged as one of the best understood model systems for elucidating the complex signaling pathways that drive chemotaxis. This review focuses on the signaling mechanisms regulating directed migration and discusses the role of polarity and development on our current understanding of this process. We highlight new findings using a second chemoattractant, folic acid and suggest that this chemical cue should be used when a developmental defect is suspected. We also speculate on recent studies which suggest that researchers should use our new understanding of the temporal and spatial relationships of signaling and cytoskeletal proteins to guide future experiments.
13 citations
TL;DR: Novel functions of the G protein alpha subunit Gα8 during vegetative and development stages are described and it is demonstrated that the increased cell-cell cohesion is mainly caused by induced CadA expression, and the induced cell-substrate adhesion is responsible for the cytokinesis defects.
4 citations