Finding Rho attractive

euronal growth cones are guided by both attractive and repulsive signals during development. Until now, one part of the guidance signaling system appeared relatively straightforward: Rac GTPases stimulate attraction, while Rho GTPases stimulate repulsion. But on page 1117, Bashaw et al. describe the activity of a new Rho guanine nucleotide exchange factor in Drosophila melanogaster , GEF64C, that can stimulate axon attraction. The authors started with flies expressing a chimeric receptor, which caused excessive crossing of the midline of the central nervous system. Overexpression of GEF64C exacerbated this phenotype. Bashaw et al. knew that the established attractants and repellents emanate from the midline, so they interpreted the new phenotye as resulting from increased attraction to the midline. GEF64C overexpression also promoted midline crossing in a mutant that otherwise shows excessive repulsion away from the midline. The GEF64C effects were diminished by a dominant-negative RhoA, but unaffected by dominant-negative Rac1 or Cdc42. It is unclear how RhoA might promote attraction. But, based on the convergence of multiple guidance signals N downstream of receptors, this type of downstream machinery presents an intriguing possibility for therapies that aim to stimulate axon regrowth in injured humans. ᭿ Excess repulsion in a Robo mutant (left) is decreased by GEF64C (right). n page 1123, Maheshwari et al. show that the way a growth factor is delivered to a cell can profoundly affect the cell's response. The work supports a new model for mammary epithelial cell migration in response to EGF stimulation, and suggests that growth factor-based therapies may be destined to fail if they are not presented to cells correctly. The authors previously developed an experimental system in which mammary epithelial cells expressing the EGF receptor (EGFR) can be stimulated by EGF through autocrine, paracrine, or intracrine mechanisms. In the new work, autocrine stimulation, in which EGF is secreted from the cells to bind its receptor on the O Turning back an invasion he ability of tumor cells to migrate through the body and invade new tissues is a major focus for research that could lead to new cancer therapies. On page 1345, Uekita et al. demonstrate that the membrane-bound matrix metalloproteinase T Internalization-defective mutants prevent invasion. MT1-MMP, which functions in both migration and invasion, must be recycled continuously from the cell surface to sustain both processes. Blocking the recycling process inhibits the invasive phenotype. Previous work had shown that MT1-MMP localizes at the migration edge, …