Fusion at the front

Fusion at the front eurite extension is dependent on the growing neurite's ability to get longer rather than fatter. Sakisaka et al. (page 17) now show that a protein called tomosyn works in a complex to help focus membrane growth to the tip of growing neurites. As neurites grow, traveling vesicles are prevented from fusing willy-nilly to the plasma membrane first by their attachment to microtubule highways. Where those highways terminate—at the back of the growth cone—is where tomosyn takes over as a fusion inhibitor. With fusion prevented, the vesicles find their way to the actin cytoskeleton, which distributes them to the leading edge of the growth cone. Sakisaka et al. found that, in growing neurites, tomosyn localizes at the rear of the growth cone. This area appears to N Anti-angiogenesis is anti-actin lood vessel growth is suppressed by several proteins—such as endorepellin—that are anti-angiogenic only after they are generated as fragments of larger proteins. Now, Bix et al. (page 97) report two surprises of endorepellin action: it exerts its effects via an integrin that collagen I uses to promote an-giogenesis; and it may operate via a heat shock protein to disassemble actin structures needed for motility. B Endorepellin is a COOH-terminal fragment of perlecan, a heparan sulfate proteoglycan that acts as a cofactor for pro-angiogenic factors such as FGF. The authors found that a segment of endorepellin was enough to prevent endothelial cell migration and formation of capillaries, and that it acted by disrupting the actin cytoskele-ton and attachment sites. They found that the major functional receptor for endorepellin was ␣ 2 ␤ 1 integrin, one of the collagen receptors. Treating cells with endorepellin resulted in clustering of ␣ 2 ␤ 1 integrin, and these integrin clusters Addition of endorepellin (right) causes activation of Hsp27 (green) and disassembly of actin stress fibers (red). be analogous to the rear of a locomoting cell. In both situations, Rho activates ROCK. The authors found that activated ROCK can, at least in vitro, phosphory-late syntaxin-1, making it a much better binding partner for tomosyn. The SNARE protein SNAP-25 also joins the complex, leading to inhibition of membrane fusion. Consistent with this suggested function in inhibiting membrane fusion, over-expressing tomosyn in neurons resulted in stunted neurites and prevented proper transport of proteins to the cell surface. Killing tomosyn expression via RNAi caused neurites to branch out excessively. Signals that induce neurite retraction, such as …