GPCR independent regulation of cell migration
This is an interesting paper from the June 2006 issue of Developmental Cell by Dandan Shan et al. This is an important paper because it implicates G13 in regulating cell migration independent of the GPCR. They start by noting that G12/13 knockout MEFs do not migrate in response to PDGF like their wild type counterparts. Ectopic expression of G13 but not G12 rescues this defect. They find that this migration proceeds through Rac because constituitively active Rac induces migration of WT MEFs but not G13 knock-out MEFs. Although this suggests that Rac works upstream of G13, other data confuses this issue. Specifically, they find that constituitively active G13 does not induce migration and more importantly they find that Rac activation is normal in the G12/13 knockout cells with respect to wild type MEFs. The key experiment of this paper involves making a G13 construct that cannot couple to the GPCR. They find that this construct like wild type G13 can rescue cell migration in the knockout background indicating that this is a receptor independent process. Biochemical analysis indicates that Rac interacts with G13-GDP, PDGF induces complex formation, and if constituitively active Rac is used PDGF is not required to induce complex formation. These data lead to a mechanism where PDGF activates Rac (possibly through a GPCR) and this then stimulates the interaction between Rac and G13. The two proteins then together regulate cell migration.
The G Protein Ga13 Is Required for Growth Factor-Induced Cell Migration
Developmental Cell 10, 707–718, June, 2006 ª2006 Elsevier Inc. DOI 10.1016/j.devcel.2006.03.014