Cortactin regulates cell migration through activation of N-WASP.
Cortactin is an actin-associated scaffolding protein that regulates cell migration. Amplification of the human gene, EMS1, has been detected in breast, head and neck tumors, where it correlates with increased invasiveness. Cortactin can regulate actin dynamics directly via its N-terminal half, which can bind and activate the Arp2/3 complex. The C-terminal portion of cortactin, however, is thought to have limited function in its regulation of the actin polymerization machinery. In this report, we identify a role for the cortactin C-terminus in regulating cell migration and, more specifically, actin dynamics. Overexpression of either full-length cortactin or cortactin C-terminus is sufficient to enhance migration of mammary epithelial cells. In vitro, cortactin binds to and activates, via its SH3 domain, a regulator of the Arp2/3 complex, neural Wiskott Aldrich Syndrome protein (N-WASP). This in vitro activation of N-WASP is likely to be important in vivo, as cortactin-enhanced migration is dependent upon N-WASP. Thus, our results suggest that cortactin has multiple mechanisms by which it can recruit and modulate the actin machinery and ultimately regulate cell migration.
Kowalski
Jennifer R
JR
Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02215, USA.
Egile
Coumaran
C
Gil
Susana
S
Snapper
Scott B
SB
Li
Rong
R
Thomas
Sheila M
SM
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D051356:Cortactin; D004847:Epithelial Cells / Q000502:physiology; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D018909:src Homology Domains
D051356:Cortactin; C495869:Cttn protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D005982:Glutathione Transferase