Physiological functions of CLAC-P/Col XXV in axon elongation and synapse formation

CLAC-P/Col XXV 在轴突伸长和突触形成中的生理功能

• 批准号: 24700373
• 负责人: WAKABAYASHI Tomoko
• 金额: $ 2.83万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24700373/
• 关键词: 運動ニューロン; 神経発生; アルツハイマー病; 分子・細胞・神経生物学

We studied the physiological functions of CLAC-P/collagen XXV, a transmembrane-type collagen originally identified as a component of senile plaque amyloid of Alzheimer's disease brains, by means of generating CLAC-P knockout and conditional knockout mice. In CLAC-P KO mice, motor axons failed to elongate and branch within the muscle, followed by degeneration of axons. Failure of muscular innervation in KO mice led to excessive apoptosis during development, resulting in almost complete and exclusive loss of spinal motoneurons. Bax deletion in CLAC-P KO mice rescued motoneurons from apoptosis, although motor axons remained halted around the muscle entry site. These observations indicate that CLAC-P/collagen XXV is a novel essential factor that regulates the initial phase of intramuscular motor innervation, which is required for subsequent target-dependent motoneuron survival and NMJ formation during development.

我们研究了CLAC-P/胶原XXV的生理功能，一种跨膜型胶原，最初被鉴定为阿尔茨海默氏病脑中老年斑淀粉样蛋白的成分，通过产生CLAC-P敲除和条件性敲除小鼠。在CLAC-P KO小鼠中，运动轴突未能在肌肉内伸长和分支，随后轴突变性。KO小鼠肌肉神经支配的失败导致发育过程中的过度凋亡，导致脊髓运动神经元几乎完全和完全丧失。Bax缺失的CLAC-P基因敲除小鼠从细胞凋亡中拯救了运动神经元，尽管运动轴突在肌肉进入位点周围仍然停止。这些观察结果表明，CLAC-P/胶原XXV是一种新的必需因子，调节肌内运动神经支配的初始阶段，这是随后的目标依赖性运动神经元存活和NMJ形成所需的发展过程中。

项目成果

ROLE OF CLAC-P/TYPE XXV COLLAGEN IN THE TERMINAL ARBORIZATION AND SURVIVAL OF DEVELOPING MOTONEURONS

CLAC-P/XXV 型胶原蛋白在发育中运动神经元的终末树枝化和存活中的作用

• 发表时间: 2013
• 作者: Tanaka T;Wakabayashi T;Oizumi H;Nishio S;Sato T;Harada A;Fujii D;Matsuo Y;Hashimoto T;Iwatsubo T.;若林朋子
• 通讯作者: 若林朋子