dictyNews Electronic Edition Volume 28, number 11 May 4, 2007 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ========= Abstracts ========= Stochastic signal processing and transduction in chemotactic response of eukaryotic cells Masahiro Ueda and Tatsuo Shibata Laboratories for Nanobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan Department of Mathematical and Life Sciences, University of Hiroshima, Higashi-Hiroshima, Hiroshima 739-8526, Japan Biophysical Journal, in press Single molecule imaging analysis of chemotactic response in eukaryotic cells has revealed a stochastic nature in the input signals and the signal transduction processes. This leads to a fundamental question on the signaling processes: how does the signaling system operate under stochastic fluctuations or noise? Here we report a stochastic model of chemotactic signaling in which noise and signal propagation along transmembrane signaling by chemoattractant receptors can be analyzed quantitatively. The results obtained from this analysis reveal that the second messenger production reactions by the receptors generate noisy signals, which contain intrinsic noise inherently generated at this reaction and extrinsic noise propagated from the ligand-receptor-binding. Such intrinsic and extrinsic noises limit directional sensing ability of chemotactic cells, which can explain the dependence of chemotactic accuracy on chemical gradients that have been observed experimentally. Our analysis also reveals regulatory mechanisms for signal improvements in the stochastically-operating signaling system by analyzing how signal-to-noise ratio (SNR) of chemotactic signals can be improved or deteriorated by the stochastic properties of receptors and second messenger molecules. Theoretical consideration of noisy signal transduction by chemotactic signaling systems can further be applied to other signaling systems in general. Submitted by: Masahiro Ueda [ueda@phys1.med.osaka-u.ac.jp] -------------------------------------------------------------------------------- Input-output relationship in galvanotactic response of Dictyostelium cells Masayuki J. Sato, Michihito Ueda, Hiroaki Takagi, Tomonobu M. Watanabe, Toshio Yanagida, and Masahiro Ueda Laboratories for Nanobiology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan. Advanced Technology Research Laboratories, Matsushita Electric Industrial Co., Ltd., 3-4 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan. Biosystems 88, 261-272. Under a direct current electric field, Dictyostelium cells exhibit migration towards the cathode direction. To determine the input-output relationship of the cell�s galvanotactic response, we developed an experimental instrument in which electric signals applied to the cells are highly reproducible and the motile response are analyzed quantitatively. With no electric field, the cells moved randomly in all directions. Upon applying an electric field, cell migration speeds became about 1.3 times faster than those in the absence of an electric field. Such kinetic effects of electric fields on the migration were observed for cells stimulated between 0.25 to 10 V/cm of the field strength. The directions of cell migrations were biased toward the cathode in a positive manner with field strength, showing galvanotactic response in a dose-dependent manner. Quantitative analysis of the relationship between field strengths and directional movements revealed that the biased movements of the cells depend on the square of electric field strength, which can be described by one simple phenomenological equation. The threshold strength for the galvanotaxis was between 0.25 and 1 V/cm. Galvanotactic efficiency reached to half-maximum at 2.6 V/cm, which corresponds to an approximately 8 mV voltage difference between the cathode and anode direction of 10 microm wide, round cells. Based on these results, possible mechanisms of galvanotaxis in Dictyostelium cells were discussed. This development of experimental system, together with its good microscopic accessibility for intracellular signaling molecules, makes Dictyostelium cells attractive as a model organism for elucidating stochastic processes in the signaling systems responsible for cell motility and its regulations. Submitted by: Masahiro Ueda [ueda@phys1.med.osaka-u.ac.jp] -------------------------------------------------------------------------------- Dictyostelium differentiation-inducing factor-1 (DIF-1) induces GLUT1 translocation and promotes glucose uptake in mammalian cells Waka Omata, Hiroshi Shibata, Msahiro Nagasawa, Itaru Kojima, Haruhisa Kikuchi, Yoshiteru Oshima, Kohei Hosaka and Yuzuru Kubohara Institute for Molecular and Cellular Regulation, Gunma University, Janan. FEBS Journal, In press The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum, while DIF-1 and its analogs have been shown to possess anti-proliferative activity in vitro in mammalian tumor cells. In the present study, we have investigated the effects of DIF-1 and its analogs on normal (non-transformed) mammalian cells. Without affecting the cell morphology and cell number, DIF-1 at micromolar levels dose-dependently promoted the glucose uptake in confluent 3T3-L1 fibroblasts, which was not inhibited with wortmannin or LY293002 [inhibitors for phosphatidylinositol 3-kinase (PI3K)]. DIF-1 affected neither the expression level of GLUT1 (glucose transporter 1) nor the activities of four key enzymes involved in glucose metabolism, such as hexokinase, fluctose-6-phosphate kinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase. Most importantly, stimulation with DIF-1 was found to induce the translocation of GLUT1 from intracellular vesicles to the plasma membranes in the cells. In differentiated 3T3-L1 adipocytes, DIF-1 induced the translocation of GLUT1 (but not of GLUT4) and promoted glucose uptake, which was not inhibited with wortmannin. These results indicate that DIF-1 induces GLUT1 translocation and thereby promotes glucose uptake, at least in part, via a PI3K/Akt-independent pathway in mammalian cells. Furthermore, analogs of DIF-1 that possess stronger anti-tumor activity than DIF-1 were less effective in promoting glucose consumption, suggesting that the mechanism of the action of DIF-1 for stimulating glucose uptake should be different from that for suppressing tumor cell growth. Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp] ============================================================ [End dictyNews, volume 28, number 11]