中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2472-2483.doi: 10.4103/1673-5374.339007

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

ADAM10通过JAMC/RAP1Gap信号通路促进神经干细胞快速循环并在脑室下区干细胞龛正确定位

  

  • 出版日期:2022-11-15 发布日期:2022-04-22

ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling

Nadia McMillan1, 2, 3, Gregory W. Kirschen4, Sanket Desai2, Emma Xia2, Stella E. Tsirka2, *, #, Adan Aguirre2, #   

  1. 1Program in Neuroscience and Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 2Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 3Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA; 4Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Stella E. Tsirka, PhD, styliani-anna.tsirka@stonybrook.edu.
  • Supported by:
    This work was supported by National Institutes of Health (NIH) Grants R01 RMH099384 (to AA) and T32GM008444 (to NM).

摘要:

目前,关于神经干细胞(NSCs)在成人脑室下区不同区域内的维持机制和谱系进程并不十分明确。静止的神经干细胞排列在脑室壁顶部区域,而有丝分裂激活的神经干细胞则分布在脑室下区的基底区、血管区域。实验发现解整合素样金属蛋白酶10在神经干细胞与室壁的结合中是必不可少的,并通过这种与顶部区域的黏附,调节神经干细胞从静止和未分化的状态切换到积极增殖和分化的细胞状态。ADAM10对连接黏附分子的处理增加了Rap1GAP的活性,这种分子机制促进了神经干细胞从顶部区域到基底区的转运和随后的谱系进程。了解负责调控神经干细胞在脑室下区干细胞龛正确定位和神经干细胞的谱系进程分子机制可以为旨在提高神经组织的再生性能的药物开发提供新的目标。

https://orcid.org/0000-0003-0022-1770 (Stella E. Tsirka)

Abstract: The mechanisms that regulate neural stem cell (NSC) lineage progression and maintain NSCs within different domains of the adult neural stem cell niche, the subventricular zone are not well defined. Quiescent NSCs are arranged at the apical ventricular wall, while mitotically activated NSCs are found in the basal, vascular region of the subventricular zone. Here, we found that ADAM10 (a disintegrin and metalloproteinase 10) is essential in NSC association with the ventricular wall, and via this adhesion to the apical domain, ADAM10 regulates the switch from quiescent and undifferentiated NSC to an actively proliferative and differentiating cell state. Processing of JAMC (junctional adhesion molecule C) by ADAM10 increases Rap1GAP activity. This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression. Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative properties of neural tissue.

Key words: ADAM10, adhesion, junctional adhesion molecule C, neural stem cells, neurogenesis, olfactory bulb, Rap1Gap, sub-ventricular zone