Actin-binding protein-1 interacts with WASp-interacting protein to regulate growth factor-induced dorsal ruffle formation.
Growth factor stimulation induces the formation of dynamic actin structures known as dorsal ruffles. Mammalian actin-binding protein-1 (mAbp1) is an actin-binding protein that has been implicated in regulating clathrin-mediated endocytosis; however, a role for mAbp1 in regulating the dynamics of growth factor-induced actin-based structures has not been defined. Here we show that mAbp1 localizes to dorsal ruffles and is necessary for platelet-derived growth factor (PDGF)-mediated dorsal ruffle formation. Despite their structural similarity, we find that mAbp1 and cortactin have nonredundant functions in the regulation of dorsal ruffle formation. mAbp1, like cortactin, is a calpain 2 substrate and the preferred cleavage site occurs between the actin-binding domain and the proline-rich region, generating a C-terminal mAbp1 fragment that inhibits dorsal ruffle formation. Furthermore, mAbp1 directly interacts with the actin regulatory protein WASp-interacting protein (WIP) through its SH3 domain. Finally, we demonstrate that the interaction between mAbp1 and WIP is important in regulating dorsal ruffle formation and that WIP-mediated effects on dorsal ruffle formation require mAbp1. Taken together, these findings identify a novel role for mAbp1 in growth factor-induced dorsal ruffle formation through its interaction with WIP.
Cortesio
Christa L
CL
Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA.
Perrin
Benjamin J
BJ
Bennin
David A
DA
Huttenlocher
Anna
A
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002154:Calpain / Q000378:metabolism; D021961:Cell Membrane Structures / Q000187:drug effects* / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051356:Cortactin; C485512:Dbnl protein, mouse; D008840:Microfilament Proteins; D009124:Muscle Proteins; D050505:Mutant Proteins; C426229:Nckipsd protein, mouse; D010982:Platelet-Derived Growth Factor; D002154:Calpain