Syntaxin 1B Suppresses Macropinocytosis and Semaphorin 3A-Induced Growth Cone Collapse
Syntaxin 1B Suppresses Macropinocytosis and Semaphorin 3A-Induced Growth Cone Collapse
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DOI：
10.1523/jneurosci.2718-10.2011
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发表时间：
2011-05-18
影响因子：
5.3
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Kabayama, Hiroyuki;Takeuchi, Makoto;Mikoshiba, Katsuhiko
生长锥塌陷是排斥性轴突引导的重要过程，并伴随着生长锥表面积的减小。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。巨胞饮症是一种不依赖于网格蛋白的内吞形式，在这种情况下，大面积的质膜可以被吞噬。我们之前报道过，鸡背根神经节神经元生长锥的巨噬细胞增多是由一种排斥性轴突引导信号蛋白3A （Sema3A）诱导的，并且Sema3A诱导的生长锥表面积和巨噬细胞液泡面积的减少是相关的，提示巨噬细胞增多在Sema3A诱导的生长锥塌陷中起积极作用。在本研究中，我们发现syntaxin 1B （Syx1B）是一种膜运输蛋白，是巨胞饮的负调控因子，其表达被Sema3A信号通路下调。巨噬细胞增多抑制剂乙基异丙基酰胺或Syx1B过表达可抑制sema3a诱导的巨噬细胞增多和生长锥塌陷。这些结果表明Syx1B将巨噬细胞介导的质膜大量内化与sema3a诱导的生长锥塌陷结合在一起。
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.