Dicty News Electronic Edition Volume 22, number 9 April 9, 2004 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 Dicty-News, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ============= Abstracts ============= Periodic signaling controlled by an oscillatory circuit that includes protein kinases ERK2 and PKA. Mineko Maeda, Sijie Lu, Gad Shaulsky, Yuji Miyazaki, Hidekazu Kuwayama, Yoshimasa Tanaka, Adam Kuspa, and William F. Loomis Department of Biology, Osaka University, Osaka, Japan; Departments of Biochemistry and Molecular Biology and Molecular and Human Genetics, Baylor College of Medicine, Houston TX; Institute of Biological Sciences, University of Tsukuba, Ibaraki, Japan; Division of Biological Sciences, University of California San Diego, La Jolla, CA Science, in press Self-regulating systems often employ robust oscillatory circuits. One such system controls the chemotactic signaling mechanism of Dictyostelium where pulses of cAMP are generated with a 7 minute periodicity. We have observed spontaneous oscillations in activation of the MAP kinase ERK2 that occur in phase with peaks of cAMP and show that ERK2 modulates cAMP levels through the phosphodiesterase RegA. Computer modeling and simulations of the underlying circuit faithfully account for the ability of the cells to spontaneously generate periodic pulses during specific stages of development. Similar oscillatory processes may occur in cells of many different species. Submitted by: Bill Loomis [wloomis@ucsd.edu] ----------------------------------------------------------------------------- A Galpha-Dependent Pathway that Antagonizes Multiple Chemoattractant Responses that Regulate Directional Cell Movement Joseph A. Brzostowski *, Carole A. Parent +, and Alan R. Kimmel * * LCDB, NIDDK, + LCMB, CCR, NCI, National Institutes of Health, Bethesda, MD 20892-8028 Genes and Development, in press Chemotactic cells, including neutrophils and Dictyostelium discoideum, orient and move directionally in very shallow chemical gradients. As cells polarize, distinct structural and signaling components become spatially constrained to the leading edge or rear of the cell. It has been suggested that complex feedback loops that function downstream of receptor signaling integrate activating and inhibiting pathways to establish cell polarity within such gradients. Much effort has focused on defining activating pathways, whereas inhibitory networks have remained largely unexplored. We have identified a novel signaling function in Dictyostelium involving a Galpha subunit (Galpha9) that antagonizes broad chemotactic response. Mechanistically, Galpha9 functions rapidly following receptor stimulation to negatively regulate PI3K/PTEN, adenylyl cyclase, and guanylyl cyclase pathways. The coordinated activation of these pathways is required to establish the asymmetric mobilization of actin and myosin that typifies polarity and ultimately directs chemotaxis. Most dramatically, cells lacking Galpha9 have extended PI(3,4,5)P3, cAMP, and cGMP responses and are hyperpolarized. In contrast, cells expressing constitutively activated Galpha9 exhibit a reciprocal phenotype. Their second message pathways are attenuated, and they have lost the ability to suppress lateral pseudopod formation. Potentially, functionally similar Galpha-mediated inhibitory signaling may exist in other eukaryotic cells to regulate chemoattractant response. Submitted by: Joseph Brzostowski [jb363a@nih.gov] ----------------------------------------------------------------------------- An Orderly Retreat: Dedifferentiation is a Regulated Process Mariko Katoh 1,4, Chad Shaw 1, Qikai Xu 1,2, Nancy Van Driessche 1,3, Takahiro Morio 4, Hidekazu Kuwayama 4, Shinji Obara 4, Hideko Urushihara 4, Yoshimasa Tanaka 4,6 and Gad Shaulsky 1,2,3,5 1 Department of Molecular and Human Genetics, 2Graduate Program in Structural and Computational Biology and Molecular Biophysics, 3 Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA 4 Institute of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan PNAS, in press (edited by Igor B. Dawid) ABSTRACT Differentiation is a highly regulated process whereby cells become specialized to perform specific functions and lose the ability to perform others. In contrast, the question of whether dedifferentiation is a genetically determined process, or merely an unregulated loss of the differentiated state, has not been resolved. We show here that dedifferentiation in the social amoeba Dictyostelium discoideum relies on a sequence of events that is independent of the original developmental state and involves the coordinated expression of a specific set of genes. A defect in one of these genes, the histidine kinase dhkA, alters the kinetics of dedifferentiation and uncouples the progression of dedifferentiation events. These observations establish dedifferentiation as a genetically determined process and suggest the existence of a developmental checkpoint that ensures a return path to the undifferentiated state. Submitted by: Gad Shaulsky [gadi@bcm.tmc.edu] =============================================================================== [End Dicty News, volume 22, number 9]