A role for VASP in RhoA-Diaphanous signalling to actin dynamics and SRF activity.
Vasodilator-stimulated phosphoprotein (VASP) is involved in multiple actin-mediated processes, including regulation of serum response factor (SRF) activity. We used the SRF transcriptional assay to define functional domains in VASP and to show that they coincide with those required for F-actin accumulation, as determined by a quantitative FACS assay. We identified inactive VASP mutants that can interfere both with F-actin assembly and with SRF activation by wild-type VASP. These VASP mutants also inhibit actin-based motility of Vaccinia virus and Shigella flexneri. VASP-induced F-actin accumulation and SRF activation require both functional Rho and its effector mDia, and conversely, mDia-mediated SRF activation is critically dependent on functional VASP. VASP and mDia also associate physically in vivo. These findings show that VASP and mDia function cooperatively downstream of Rho to control F-actin assembly and SRF activity.
Grosse
Robert
R
Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, Transcription Laboratory, Room 401, 44 Lincoln's Inn Fields, London.
Copeland
John W
JW
Newsome
Timothy P
TP
Way
Michael
M
Treisman
Richard
R
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D012763:Shigella flexneri / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014616:Vaccinia virus / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D001798:Blood Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491464:Diap1 protein, mouse; D000080865:Formins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D026362:Serum Response Factor; D000098662:Vasodilator-Stimulated Phosphoprotein; D020742:rhoA GTP-Binding Protein