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DRIVEN TO THE BRINK BY A G PROTEIN

Gi3 (yellow) clusters at the leading edge (arrows) of a crawling cell.

Missing links aren't just for paleontologists. Ghosh et al. report what might be the long-sought connection between cell surface receptors and the direction in which cells crawl.

Nearby food and growth factors galvanize a cell. At the section of the membrane nearest the stimulus, activity of the signaling molecule Akt cranks up and actin elongates into stress fibers essential for crawling. The cell then pushes forward this part of its membrane, the leading edge. Surface receptors first detect the stimulus, and then trigger G proteins, which pass the signal on. What scientists don't know is how cells confine the molecular action to the leading edge. The team suspected it might involve an intermediary, the protein GIV, which can latch onto G proteins and stimulate Akt.

To find out, Ghosh et al. investigated the interaction between GIV and a G protein component known as Gi3. If Gi3 is absent, the team found, actin doesn't extend, Akt activity doesn't rev up, and cells are stuck. Gi3 homes in on the leading edge, and it appears to drag GIV along with it. In cells lacking Gi3, GIV collects near the Golgi apparatus instead of dispersing to the edge of the cell. Gi3 might even instigate a positive feedback loop because it presents GIV to Akt to be switched on; GIV can then further amplify Akt activity.

GIV and Gi3 also help macrophages and tumor cells migrate, the team found. By ferrying GIV to the leading edge, Gi3 might ensure that only one portion of the membrane undergoes the changes required for movement.

Ghosh, P., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200712066.[Abstract/Free Full Text]

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 837K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Social Bookmarking                            What's this?