Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and IQGAP-related proteins.
Cytokinesis in eukaryotic organisms is under the control of small GTP-binding proteins, although the underlying molecular mechanisms are not fully understood. Cortexillins are actin-binding proteins whose activity is crucial for cytokinesis in Dictyostelium. Here we show that the IQGAP-related and Rac1-binding protein DGAP1 specifically interacts with the C-terminal, actin-bundling domain of cortexillin I. Like cortexillin I, DGAP1 is enriched in the cortex of interphase cells and translocates to the cleavage furrow during cytokinesis. The activated form of the small GTPase Rac1A recruits DGAP1 into a quaternary complex with cortexillin I and II. In DGAP1(-) mutants, a complex can still be formed with a second IQGAP-related protein, GAPA. The simultaneous elimination of DGAP1 and GAPA, however, prevents complex formation and localization of the cortexillins to the cleavage furrow. This leads to a severe defect in cytokinesis, which is similar to that found in cortexillin I/II double-null mutants. Our observations define a novel and functionally significant signaling pathway that is required for cytokinesis.
Faix
J
J
Department of Physiology, University of Wisconsin-Madison, 1300 University Avenue, WI 53706, USA. faix@physiology.wisc.edu
Weber
I
I
Mintert
U
U
Köhler
J
J
Lottspeich
F
F
Marriott
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D017931:DNA Primers; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D009154:Mutation; D010449:Peptide Mapping; D011233:Precipitin Tests; D015800:Protozoan Proteins; D011721:Pyrenes / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D017931:DNA Primers; C101203:IQ motif containing GTPase activating protein 1; D008840:Microfilament Proteins; D015800:Protozoan Proteins; D011721:Pyrenes; C101109:ctxA protein, Dictyostelium discoideum; D020703:ras GTPase-Activating Proteins; C068172:N-(deoxyguanosin-8-yl)-2-aminopyrene; D003849:Deoxyguanosine