title: Local Ras activation, PTEN pattern, and global actin flow in the chemotactic responses of oversized cells.
abstract: Chemotactic responses of eukaryotic cells require a signal processing system that translates an external gradient of attractant into directed motion. To challenge the response system to its limits, we increased the size of Dictyostelium discoideum cells by using electric-pulse-induced fusion. Large cells formed multiple protrusions at different sites along the gradient of chemoattractant, independently turned towards the gradient and competed with each other. Finally, these cells succeeded to re-establish polarity by coordinating front and tail activities. To analyse the responses, we combined two approaches, one aimed at local responses by visualising the dynamics of Ras activation at the front regions of reorientating cells, the other at global changes of polarity by monitoring front-to-tail-directed actin flow. Asymmetric Ras activation in turning protrusions underscores that gradients can be sensed locally and translated into orientation. Different to cells of normal size, the polarity of large cells is not linked to an increasing front-to-tail gradient of the PIP3-phosphatase PTEN. But even in large cells, the front communicates with the tail through an actin flow that might act as carrier of a protrusion inhibitor.
authors: Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany.
authors: Markus
authors: M
authors: Lange
authors: Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany.
authors: Jana
authors: J
authors: Prassler
authors: Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany.
authors: Mary
authors: M
authors: Ecke
authors: LMU Munich, Department of Cell Biology (Anatomy III), BioMedical Center, Großhaderner Str. 9, Martinsried D-82152, Germany.
authors: Annette
authors: A
authors: Müller-Taubenberger
authors: Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany gerisch@biochem.mpg.de.
authors: Günther
authors: 0000-0002-8348-1924
authors: G
authors: Gerisch
mesh_terms: D000199:Actins / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D022081:Cell Surface Extensions / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004058:Diffusion; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010873:Pinocytosis / Q000187:drug effects; D012212:Rheology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D002630:Chemotactic Factors; D000242:Cyclic AMP; D051059:PTEN Phosphohydrolase; D018631:ras Proteins
keywords: Actin flow; Cell fusion; Cell polarity; Chemotaxis; PTEN; Ras