title: Guanylyl cyclase protein and cGMP product independently control front and back of chemotaxing Dictyostelium cells.
abstract: Chemotaxis of amoeboid cells is driven by actin filaments in leading pseudopodia and actin-myosin filaments in the back and at the side of the cell to suppress pseudopodia. In Dictyostelium, cGMP plays an important role during chemotaxis and is produced predominantly by a soluble guanylyl cyclase (sGC). The sGC protein is enriched in extending pseudopodia at the leading edge of the cell during chemotaxis. We show here that the sGC protein and the cGMP product have different functions during chemotaxis, using two mutants that lose either catalytic activity (sGCDelta cat) or localization to the leading edge (sGCDeltaN). Cells expressing sGCDeltaN exhibit excellent cGMP formation and myosin localization in the back of the cell, but they exhibit poor orientation at the leading edge. Cells expressing the catalytically dead sGCDelta cat mutant show poor myosin localization at the back, but excellent localization of the sGC protein at the leading edge, where it enhances the probability that a new pseudopod is made in proximity to previous pseudopodia, resulting in a decrease of the degree of turning. Thus cGMP suppresses pseudopod formation in the back of the cell, whereas the sGC protein refines pseudopod formation at the leading edge.
authors.affiliation: Department of Biology, University of Groningen, 9751 NN Haren, The Netherlands.
authors.forename: Douwe M
authors.initials: DM
authors.lastname: Veltman
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006162:Guanylate Cyclase; D050505:Mutant Proteins / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D000199:Actins; D050505:Mutant Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000242:Cyclic AMP; D009218:Myosins; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP