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

Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites
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DOI:
10.1083/jcb.200405002
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发表时间:
2004-07-05
影响因子:
7.8
通讯作者:
Takai, Y
Takai, Y
中科院分区:
生物学1区
文献类型:
--
作者:
Sakisaka, T;Baba, T;Takai, Y

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神经突起的延伸需要依赖于圈套的质膜前体小泡与生长锥的质膜融合。在这里,我们发现Tomosyn定位于生长锥的掌心,并抑制那里的囊泡融合,从而促进囊泡向生长锥前缘的质膜运输。Tomosyn的定位是因为被Rho小G蛋白激活的岩石磷酸化了Synaxin-1,从而增加了Synaxin-1对Tomosyn的亲和力,并与Tomosyn形成了稳定的复合体,从而抑制了SNARE复合体的形成。在轴突的回缩过程中,Tomosyn分布在轴突的边缘,并抑制囊泡与质膜的融合。因此,Tomosyn通过与ROCK磷酸化的Synaxin-1结合来划分质膜,从而调节神经突起的伸展和收缩。
Extension of neurites requires the SNARE-dependent fusion of plasmalemmal precursor vesicles with the plasma membrane of growth cones. Here, we show that tomosyn localizes at the palm of growth cones and inhibits the fusion of the vesicles there, thus promoting transport of the vesicles to the plasma membrane of the leading edges of growth cones. Tomosyn localizes because ROCK activated by Rho small G protein phosphorylates syntaxin-1, which increases the affinity of syntaxin-1 for tomosyn and forms a stable complex with tomosyn, resulting in inhibition of the formation of the SNARE complex. In retraction of neurites, tomosyn localizes all over the edges of the neurites and inhibits fusion of the vesicles with the plasma membrane. Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites.