SUN2 regulates mitotic duration in response to extracellular matrix rigidity.

SUN2 regulates mitotic duration in response to extracellular matrix rigidity.
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DOI:
10.1073/pnas.2116167119
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发表时间:
2022-11-08
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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在生理条件下,细胞感知到许多影响其生长的信号。在这里,我们观察到细胞微环境的机械特性控制细胞分裂的进程。我们发现,当在刚性增加的基质上培养时,细胞分裂得更快。该机制涉及核蛋白 SUN2,其表达因基质刚性而上调,进而通过促进中期到后期的转变来加速有丝分裂。细胞如何调整其生长以适应周围环境的空间和机械限制是生物学许多方面的核心。在这里,我们研究了细胞外基质 (ECM) 刚性如何影响细胞分裂。我们发现,在刚性基质上培养时,细胞分裂得更快。虽然我们观察到 ECM 刚性对圆整或有丝分裂后扩散持续时间没有影响,但我们发现基质刚性的变化会影响有丝分裂进展。我们注意到,ECM 弹性上调核骨架和细胞骨架连接体 (LINC) 复合物成分 SUN2 的表达,进而通过作用于有丝分裂纺锤体形成促进中期到后期的转变,而当细胞粘附到软 ECM 时,低水平的 SUN2 表达会扰乱星体微管组织并延迟后期的开始。
Under physiological conditions, there are numerous signals perceived by cells that influence their growth. Here, we observed that the mechanical properties of the cellular microenvironment control the progression of cell division. We found that cells divide more rapidly when cultured on substrates with increasing rigidity. This mechanism involves the nuclear protein SUN2, whose expression is up-regulated by matrix rigidity and in turn accelerates mitosis by promoting metaphase-to-anaphase transition. How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates. While we observed no effect of ECM rigidity on rounding or postmitotic spreading duration, we found that changes in matrix stiffness impact mitosis progression. We noticed that ECM elasticity up-regulates the expression of the linker of nucleoskeleton and cytoskeleton (LINC) complex component SUN2, which in turn promotes metaphase-to-anaphase transition by acting on mitotic spindle formation, whereas when cells adhere to soft ECM, low levels of SUN2 expression perturb astral microtubule organization and delay the onset of anaphase.
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