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N-钙黏蛋白通过肌动蛋白细胞骨架重塑对果蝇神经胶质细胞的集体迁移起负向调节作用。

N-cadherin negatively regulates collective Drosophila glial migration through actin cytoskeleton remodeling.

作者信息

Kumar Arun, Gupta Tripti, Berzsenyi Sara, Giangrande Angela

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France Centre National de la Recherche Scientifique, UMR7104, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France Université de Strasbourg, Illkirch, France.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France Centre National de la Recherche Scientifique, UMR7104, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France Université de Strasbourg, Illkirch, France

出版信息

J Cell Sci. 2015 Mar 1;128(5):900-12. doi: 10.1242/jcs.157974. Epub 2015 Jan 15.

Abstract

Cell migration is an essential and highly regulated process. During development, glia cells and neurons migrate over long distances - in most cases collectively - to reach their final destination and build the sophisticated architecture of the nervous system, the most complex tissue of the body. Collective migration is highly stereotyped and efficient, defects in the process leading to severe human diseases that include mental retardation. This dynamic process entails extensive cell communication and coordination, hence, the real challenge is to analyze it in the entire organism and at cellular resolution. We here investigate the impact of the N-cadherin adhesion molecule on collective glial migration, by using the Drosophila developing wing and cell-type specific manipulation of gene expression. We show that N-cadherin timely accumulates in glial cells and that its levels affect migration efficiency. N-cadherin works as a molecular brake in a dosage-dependent manner, by negatively controlling actin nucleation and cytoskeleton remodeling through α/β catenins. This is the first in vivo evidence for N-cadherin negatively and cell autonomously controlling collective migration.

摘要

细胞迁移是一个至关重要且受到高度调控的过程。在发育过程中,神经胶质细胞和神经元会进行长距离迁移——大多数情况下是集体迁移——以到达它们的最终目的地,并构建出神经系统这一身体最复杂组织的精细结构。集体迁移具有高度的模式化和高效性,该过程中的缺陷会导致包括智力迟钝在内的严重人类疾病。这个动态过程需要广泛的细胞通讯和协调,因此,真正的挑战是在整个生物体中并以细胞分辨率对其进行分析。我们在此通过利用果蝇发育中的翅膀以及基因表达的细胞类型特异性操纵,研究N-钙黏蛋白黏附分子对神经胶质细胞集体迁移的影响。我们发现N-钙黏蛋白会在神经胶质细胞中适时积累,并且其水平会影响迁移效率。N-钙黏蛋白通过α/β连环蛋白负向控制肌动蛋白成核和细胞骨架重塑,以剂量依赖的方式作为分子制动器发挥作用。这是N-钙黏蛋白负向且细胞自主控制集体迁移的首个体内证据。

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