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Neurite 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.3 v: h) v1 A* [+ O4 A
. ? O+ j* U$ q4 f K. n: dAs 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.5 w) o9 z! o% g3 H
* O. H9 x( E5 R0 D+ {Sakisaka et al. found that, in growing neurites, tomosyn localizes at the rear of the growth cone. This area appears to 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, phosphorylate 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.) f1 B3 r+ c! ?0 [
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Consistent with this suggested function in inhibiting membrane fusion, overexpressing 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.
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Signals that induce neurite retraction, such as LPA, activate ROCK throughout the growth cone. This resulted in distribution of tomosyn—and presumably inhibition of fusion—throughout the growth cone. Actin contractility should then be free to reel in the existing plasma membrane as the neurite retracts.(Tomosyn (green) inhibits vesicle fusion ) |
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发表于 2009-3-6 08:11
发表于 2015-6-10 10:10
