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Fusion at the front

Tomosyn (green) inhibits vesicle fusion so that it only occurs at the extreme ends of neurites (red, labeled with Sec8).

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.

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 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.

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.

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.

Aparna Sreenivasan

aparnas{at}nasw.org

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Related Article

Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites

Toshiaki Sakisaka, Takeshi Baba, Shintaro Tanaka, Genkichi Izumi, Masato Yasumi, and Yoshimi Takai
J. Cell Biol. 2004 166: 17-25. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 717K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sreenivasan, A. Search for Related Content PubMed Articles by Sreenivasan, A. Related Collections Related Article Social Bookmarking                            What's this?