Linking Ras to myosin function: RasGEF Q, a Dictyostelium exchange factor for RasB, affects myosin II functions.
Ras guanine nucleotide exchange factor (GEF) Q, a nucleotide exchange factor from Dictyostelium discoideum, is a 143-kD protein containing RasGEF domains and a DEP domain. We show that RasGEF Q can bind to F-actin, has the potential to form complexes with myosin heavy chain kinase (MHCK) A that contain active RasB, and is the predominant exchange factor for RasB. Overexpression of the RasGEF Q GEF domain activates RasB, causes enhanced recruitment of MHCK A to the cortex, and leads to cytokinesis defects in suspension, phenocopying cells expressing constitutively active RasB, and myosin-null mutants. RasGEF Q(-) mutants have defects in cell sorting and slug migration during later stages of development, in addition to cell polarity defects. Furthermore, RasGEF Q(-) mutants have increased levels of unphosphorylated myosin II, resulting in myosin II overassembly. Collectively, our results suggest that starvation signals through RasGEF Q to activate RasB, which then regulates processes requiring myosin II.
Mondal
Subhanjan
S
Centre for Biochemistry, Institute of Biochemistry I, Medical Faculty and Centre for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
Bakthavatsalam
Deenadayalan
D
Steimle
Paul
P
Gassen
Berthold
B
Rivero
Francisco
F
Noegel
Angelika A
AA
D000199:Actins / Q000737:chemistry; D000818:Animals; D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D005821:Genetic Techniques; D008027:Light; D008954:Models, Biological; D024462:Myosin Type II / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*
D000199:Actins; D011993:Recombinant Fusion Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D000242:Cyclic AMP; D024462:Myosin Type II; D009218:Myosins; D018631:ras Proteins