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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19700302/
• 关键词: マクロピノサイトーシス; 成長円錐退縮; 反発性軸索誘導; syntaxin1B; Neurotoxin C1; Syntaxin1; 反発性軸策誘導; セマフォリン; カルシウム; 軸索ガイダンス; カルシウムストア; 神経突起伸長

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.

生长锥塌陷是排斥轴突引导的关键过程，并伴随着生长锥表面积的减少。这种减少的过程可能会受到内吞作用的调节。但是，其分子机制尚不清楚。大型细胞增多症是一种独立于网格蛋白的内吞作用形式，其中大面积的质膜可以吞噬。我们先前已经报道说，通过闪存蛋白3a（SEMA3A）（一种排斥的轴突引导提示）以及SEMA3A诱导的生长锥面积和大型液泡区域的生长锥面积的减少，表明呈阳性的角色，促进了大型细胞性细胞增多症在鸡背根神经节神经元的生长锥中，sema3a（sema3a）（sema3a）和Sema3a诱导的生长锥面积和大型液泡区域的阳性作用均具有良好的作用。 坍塌。在本研究中，我们发现语法1B（SYX1B）是一种膜运输蛋白，是大胞吐作用的阴性调节剂，其表达被SEMA3A信号传导下调。大胞症抑制剂乙基异丙基胺或SYX1B过表达抑制了SEMA3A诱导的巨细胞增多症和生长锥塌陷。这些结果表明，Syx1b夫妇大胞胞细胞增多介导的质膜大规模内在化对SEMA3A诱导的生长锥塌陷。

项目成果

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。

• 发表时间: 2011
• 期刊: The Journal of Neuroscience. 31(20)
• 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

• DOI: 10.1016/j.mcn.2008.08.009
• 发表时间: 2009-01-05
• 期刊: MOLECULAR AND CELLULAR NEUROSCIENCE
• 影响因子: 3.5
• 作者: Kabayama, Hiroyuki;Nakamura, Takeshi;Mikoshiba, Katsuhiko
• 通讯作者: Mikoshiba, Katsuhiko