title: Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-beta-dependent actin reorganization and migration.
abstract: BACKGROUND
  The F-BAR {Fes/CIP4 [Cdc42 (cell division cycle 42)-interacting protein 4] homology and BAR (Bin/amphiphysin/Rvs)} proteins have emerged as important co-ordinators of signalling pathways that regulate actin assembly and membrane dynamics. The presence of the F-BAR domain is the hallmark of this family of proteins and the CIP4 (Cdc42-interacting protein 4) was one of the first identified vertebrate F-BAR proteins. There are three human CIP4 paralogues, namely CIP4, FBP17 (formin-binding protein 17) and Toca-1 (transducer of Cdc42-dependent actin assembly 1). The CIP4-like proteins have been implicated in Cdc42-dependent actin reorganization and in regulation of membrane deformation events visible as tubulation of lipid bilayers.
  
  
  RESULTS
  We performed side-by-side analyses of the three CIP4 paralogues. We found that the three CIP4-like proteins vary in their effectiveness to catalyse membrane tubulation and actin reorganization. Moreover, we show that the CIP4-dependent membrane tubulation is enhanced in the presence of activated Cdc42. Some F-BAR members have been shown to have a role in the endocytosis of the EGF (epidermal growth factor) receptor and this prompted us to study the involvement of the CIP4-like proteins in signalling of the PDGFRbeta [PDGF (platelet-derived growth factor) beta-receptor]. We found that knock-down of CIP4-like proteins resulted in a prolonged formation of PDGF-induced dorsal ruffles, as well as an increased PDGF-dependent cell migration. This was most likely a consequence of a sustained PDGFRbeta activation caused by delayed internalization of the receptor in the cells treated with siRNA (small interfering RNA) specific for the CIP4-like proteins.
  
  
  CONCLUSIONS
  Our findings show that CIP4-like proteins induced membrane tubulation downstream of Cdc42 and that they have important roles in PDGF-dependent actin reorganization and cell migration by regulating internalization and activity of the PDGFRbeta. Moreover, the results suggest an important role for the CIP4-like proteins in the regulation of the activity of the PDGFRbeta.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Box 280, SE-17177 Stockholm, Sweden.
authors.forename: Marcia
authors.initials: M
authors.lastname: Toguchi
authors.forename: Ninna
authors.initials: N
authors.lastname: Richnau
authors.forename: Aino
authors.initials: A
authors.lastname: Ruusala
authors.forename: Pontus
authors.initials: P
authors.lastname: Aspenström
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; C433770:FNBP1 protein, human; C482527:FNBP1L protein, human; D050556:Fatty Acid-Binding Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human; D020797:Receptor, Platelet-Derived Growth Factor beta; D020764:cdc42 GTP-Binding Protein