法国巴黎文理研究大学M. Piel和瑞士苏黎世联邦理工学院D. J. Müller课题组合作取得一项新突破。他们的研究发现细胞核在对空间限制的反应中起决定性作用。相关论文于2020年10月16日发表于国际学术期刊《科学》。
在本研究中,研究人员发现细胞通过使用其最大和最坚硬的细胞器-细胞核来测量空间限制的程度。小于静息状态下细胞核大小的细胞会发生细胞核形变,从而扩大并伸展其包膜。这通过核被膜拉伸敏感蛋白激活了对放线菌素皮质的信号传导,从而上调细胞的收缩能力。
研究人员确定了以细胞核为标尺的收缩反应信号传导途径,其参与调控细胞迁移行为。细胞依靠细胞核标尺调节动力,使其能够通过复杂三维环境中的限制性空隙,这是与癌细胞入侵、免疫反应和胚胎发育相关的过程。
据了解,后生生物体内微观环境非常拥挤。尚不清楚单个细胞是否可以针对有限的空间调整其行为。
附:英文原文
Title: The nucleus acts as a ruler tailoring cell responses to spatial constraints
Author: A. J. Lomakin, C. J. Cattin, D. Cuvelier, Z. Alraies, M. Molina, G. P. F. Nader, N. Srivastava, P. J. Saez, J. M. Garcia-Arcos, I. Y. Zhitnyak, A. Bhargava, M. K. Driscoll, E. S. Welf, R. Fiolka, R. J. Petrie, N. S. De Silva, J. M. González-Granado, N. Manel, A. M. Lennon-Duménil, D. J. Müller, M. Piel
Issue&Volume: 2020/10/16
Abstract: The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler–based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
DOI: 10.1126/science.aba2894
Source: https://science.sciencemag.org/content/370/6514/eaba2894