RRC ID 29043
Author Bosgraaf L, Russcher H, Smith JL, Wessels D, Soll DR, Van Haastert PJ.
Title A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium.
Journal EMBO J
Abstract Chemotactic stimulation of Dictyostelium cells results in a transient increase in cGMP levels, and transient phosphorylation of myosin II heavy and regulatory light chains. In Dictyostelium, two guanylyl cyclases and four candidate cGMP-binding proteins (GbpA- GbpD) are implicated in cGMP signalling. GbpA and GbpB are homologous proteins with a Zn2+-hydrolase domain. A double gbpA/gbpB gene disruption leads to a reduction of cGMP-phosphodiesterase activity and a 10-fold increase of basal and stimulated cGMP levels. Chemotaxis in gbpA(-)B(-) cells is associated with increased myosin II phosphorylation compared with wild-type cells; formation of lateral pseudopodia is suppressed resulting in enhanced chemotaxis. GbpC is homologous to GbpD, and contains Ras, MAPKKK and Ras-GEF domains. Inactivation of the gbp genes indicates that only GbpC harbours high affinity cGMP-binding activity. Myosin phosphorylation, assembly of myosin in the cytoskeleton as well as chemotaxis are severely impaired in mutants lacking GbpC and GbpD, or mutants lacking both guanylyl cyclases. Thus, a novel cGMP signalling cascade is critical for chemotaxis in Dictyostelium, and plays a major role in myosin II regulation during this process.
Volume 21(17)
Pages 4560-70
Published 2002-9-2
DOI 10.1093/emboj/cdf438
PMID 12198158
PMC PMC126179
MeSH 3',5'-Cyclic-AMP Phosphodiesterases / genetics 3',5'-Cyclic-AMP Phosphodiesterases / metabolism Animals Carrier Proteins / metabolism Chemotaxis / physiology Cyclic GMP / physiology* Cytoskeleton / metabolism Dictyostelium / drug effects Dictyostelium / genetics Dictyostelium / physiology* Guanylate Cyclase / genetics Guanylate Cyclase / metabolism Intracellular Signaling Peptides and Proteins* Myosin Type II / metabolism* Phosphorylation Protein Processing, Post-Translational Protozoan Proteins / genetics Protozoan Proteins / metabolism* Second Messenger Systems / physiology*
IF 9.889
Times Cited 115
Cellular slime molds S00008 S00010 S00142 S00143 S00338 S00339 S00340