When cargos jump tracks

Cancer cells straighten out W hen a cancer cell hangs a left, it needs the protein cofi lin. As Sidani et al. report, cofi lin helps wandering cancer cells change course by enabling them to turn. Cofi lin is important for cells on the go. As a cell crawls, actin fi bers at its front edge polymerize, pushing the membrane forward. Cofi lin promotes the elongation of these fi bers by breaking them: the fresh ends double the number of attachment points for other actin segments and lure the Arp2/3 complex, which hops on and extends the fi bers. Although researchers have worked out some of cofi lin’s functions, they didn’t have a comprehensive picture of how the protein infl uences cell movement. Sidani et al. knocked out the protein in a line of aggressive mouse mammary tumor cells. Instead of moving in random directions, the cells crawled straight ahead, rarely turning. The knockout cells sent out fewer lamellipodia, the extensions they use to probe their environment, and the lamellipodia they did produce were stickier, thus inhibiting course changes. By breaking actin fi bers, cofi lin draws the Arp2/3 complex to different locations at the cell edge. New lamellipodia sprout at these spots, and the cell shifts direction. Without cofi lin, Arp2/3 piles up at the front of the cell, which only goes forward. The researchers have already shown that quashing cofi lin activity leashed wandering tumor cells, suggesting that cofi linblocking drugs will do the same. Reference: Sidani, M., et al. 2007. J. Cell Biol. 179:777–791. Fusion in three easy steps M ating is complicated for yeast. The nuclei of two cells have to get together, even though both nuclear membranes remain intact. Melloy et al. now nail down how many steps it takes for the cells to combine their nuclei. Before human gametes fuse, their nuclear membranes break down to allow the nuclear contents to mix. But when yeast mate, the inner and outer membranes of the two nuclei have to join, as do the spindle pole bodies (SPBs). Spanning the inner and outer membranes, SPBs anchor the microtubules that winch the nuclei together. Whether the components merge simultaneously or in three separate steps has been debated, due to the diffi culty of catching nuclei in the act. Melloy et al. used electron tomography to capture 3D images of nuclei at different stages of fusion. They found that nuclei retained separate SPBs even after the inner and outer membranes had joined, indicating that the SPBs are the last to fuse. To determine which membranes linked up first, the team turned to light microscopy. They filled the nucleus with one marker and the lumen between the inner and outer membranes with another. The lumen marker started moving from one partner to the other about 30 seconds before the nuclear marker, indicating that the outer membranes merge fi rst. Researchers suspect that outer membranes are drawn together by SNARE proteins. The mystery now is which proteins join the inner membranes. Reference: Melloy, P., et al. 2007. J. Cell Biol. 179:659–670.