The role of macropinocytosis in repulsive axon guidance

巨胞饮作用在排斥性轴突引导中的作用

基本信息

批准号：
19700302
负责人：
KABAYAMA Hiroyuki
金额：
$ 2.51万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2010
项目状态：
已结题

项目摘要

Growth cone collapse is a crucial process for repulsive axon guidance and is accompanied by a reduction in growth cone surface area. This process of reduction may be regulated by endocytosis; however, its molecular mechanism is unclear. Macropinocytosis is a clathrin-independent form of endocytosis in which large areas of plasma membrane can be engulfed. We have reported previously that macropinocytosis is induced in growth cones of chick dorsal root ganglion neurons by semaphorin 3A (Sema3A), a repulsive axon guidance cue, and that Sema3A-induced reduction in growth cone surface area and macropinocytic vacuole area were correlated, suggesting a positive role for macropinocytosis in Sema3A-induced growth cone collapse. In the present study, we found that syntaxin 1B (Syx1B), a membrane trafficking protein, is a negative regulator of macropinocytosis, and its expression is downregulated by Sema3A signaling. Macropinocytosis inhibitor ethylisopropylamiloride or Syx1B overexpression suppressed Sema3A-induced macropinocytosis and growth cone collapse. These results indicate that Syx1B couples macropinocytosis-mediated massive internalization of the plasma membrane to Sema3A-induced growth cone collapse.

生长锥塌陷是排斥性轴突引导的关键过程，并伴随着生长锥表面积的减少。这种还原过程可能受到内吞作用的调节。然而，其分子机制尚不清楚。巨胞饮作用是一种不依赖于网格蛋白的内吞作用，其中大面积的质膜可以被吞噬。我们之前报道过，信号蛋白 3A (Sema3A)（一种排斥性轴突引导信号）在鸡背根神经节神经元的生长锥中诱导巨胞饮作用，并且 Sema3A 诱导的生长锥表面积和巨胞饮液泡面积的减少是相关的，这表明巨胞饮作用在 Sema3A 诱导的生长锥塌陷中发挥积极作用。在本研究中，我们发现突触蛋白1B（Syx1B）是一种膜运输蛋白，是巨胞饮作用的负调节因子，其表达被Sema3A信号传导下调。大胞饮作用抑制剂乙基异丙基阿米洛利或 Syx1B 过表达抑制了 Sema3A 诱导的大胞饮作用和生长锥塌陷。这些结果表明 Syx1B 将巨胞饮作用介导的质膜大量内化与 Sema3A 诱导的生长锥塌陷结合起来。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Syntaxin 1B suppresses macropinocytosis and Sema3a-induced growth cone collapse.

Syntaxin 1B 抑制巨胞饮作用和 Sema3a 诱导的生长锥塌陷。

DOI：
发表时间：
2011
期刊：
The Journal of Neuroscience. 31(20)
影响因子：
0
作者：
Kabayama H;Takeuchi M;Taniguchi M;Tokushige N;Kozaki S;Mizutani A;Mikoshiba K.
通讯作者：
Mikoshiba K.

Ca2+ induces macropinocytosis via F-actin depolymerization during growth cone collapse