Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-beta-dependent actin reorganization and migration

Biol Cell. 2010 Jan 14;102(4):215-30. doi: 10.1042/BC20090033.

Abstract

Background information: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Carrier Proteins / metabolism
  • Cattle
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Movement
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Minor Histocompatibility Antigens
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • Actins
  • Carrier Proteins
  • FNBP1 protein, human
  • FNBP1L protein, human
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • TRIP10 protein, human
  • Receptor, Platelet-Derived Growth Factor beta
  • cdc42 GTP-Binding Protein