Editors' ChoiceCell Biology

Linking Arf to Membrane Ruffles

Science's STKE  01 Dec 1999:
Vol. 1999, Issue 10, pp. tw1
DOI: 10.1126/stke.1999.10.tw1

In response to certain growth factors, cells reorganize their actin cytoskeleton, sometimes causing ruffling of their surface plasma membrane. Because the phospholipid phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] binds to certain actin-binding proteins, it has been implicated in signaling pathways that mediate this response. Although members of the Rho family of small GTP-binding proteins are thought to stimulate PI(4,5)P2 production in cells, Honda et al. report that another small GTP-binding protein, ARF6, may also regulate PI(4,5)P2 in cells by stimulating the α isoform of phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5Kα]. When overexpressed in cells that were then stimulated with epidermal growth factor, ARF6 and PI(4)P5Kα colocalized to membrane ruffles. Phospholipase D2, which generates phosphatidic acid (PA), also localized to membrane ruffles. PA had a synergistic effect on the stimulation of PI(4)P5Kα by ARF6 in vitro. The authors suggest that an ARF6-dependent pathway regulates membrane ruffling and may work in parallel to regulatory pathways that depend on rho-related proteins.

Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A.J., Frohman, M.A., and Kanaho, Y. (1999) Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99: 521-532. [Online Journal]