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Volume 271, Number 39, Issue of September 27, 1996 pp. 23718-23724
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Regulation of Guanylyl Cyclase by a cGMP-binding Protein during Chemotaxis in Dictyostelium discoideum

(Received for publication, May 9, 1996, and in revised form, July 10, 1996)

From the Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands

Chemoattractants transiently activate guanylyl cyclase in Dictyostelium discoideum cells. Mutant analysis demonstrates that the produced cGMP plays an essential role in chemotactic signal transduction, controlling the actomyosin-dependent motive force. Guanylyl cyclase activity is associated with the particulate fraction of a cell homogenate. The addition of the cytosol stimulates guanylyl cyclase activity, whereas the cytosol plus ATP/Mg²⁺ inhibits enzyme activity. We have analyzed the regulation of guanylyl cyclase in chemotactic mutants and present evidence that a cGMP-binding protein mediates both stimulation and ATP-dependent inhibition of guanylyl cyclase.

Upon chromatography of cytosolic proteins, cGMP binding activity co-elutes with both guanylyl cyclase-stimulating and ATP-dependent-inhibiting activities. In addition, ATP-dependent inhibition of guanylyl cyclase activity is enhanced by the cGMP analogue 8-Br-cGMP, suggesting that a cGMP-binding protein regulates guanylyl cyclase activity. Mutant KI-4 has an aberrant cGMP binding activity with very low K_d and shows a very small chemoattractant-mediated cGMP response; the cytosol from this mutant does not stimulate guanylyl cyclase. In contrast to KI-4, the aberrant cGMP binding activity of mutant KI-7 has a very high K_d and chemoattractants induce a prolonged cGMP response. The cytosol of this mutant stimulates guanylyl cyclase activity, but ATP does not inhibit the enzyme. Thus, two previously isolated chemotactic mutants are defective in the activation and inhibition of guanylyl cyclase, respectively. The positive and negative regulation of guanylyl cyclase by its product cGMP may well explain how cells process the temporospatial information of chemotactic signals, which is necessary for sensing the direction of the chemoattractant.

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