十字路口上的生命:核 LINC 复合物与血管机械传导

P. Bougaran, V. Bautch
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引用次数: 0

摘要

血管内皮细胞位于所有血管的内表面,它们在整个生命周期中都暴露在极化机械力的作用下。基底基质相互作用和顶端血流诱导的剪切应力调节着血管的发育、重塑和血管稳态的维持。这些相互作用的破坏会导致功能障碍和血管病变,但人们对如何感知和整合作用力以影响内皮细胞的行为还知之甚少。最近,内皮细胞核成为一个重要的力传导细胞器,它通过与细胞-细胞和细胞-基质连接点之间的通讯参与血管机械传导。由 SUN 蛋白和 nesprin 蛋白组成的 LINC 复合物横跨核膜,并连接核薄层、核膜和细胞骨架。在此,我们回顾了 LINC 复合物参与内皮细胞机械传导的情况,描述了每个 LINC 复合物成分的独特和重叠功能,并考虑了新出现的证据,即两个主要的 SUN 蛋白 SUN1 和 SUN2 协调了复杂的相互作用,向外延伸到细胞-细胞和细胞-基质连接处,向内延伸到细胞核和染色质内的相互作用。我们将这些发现与血管病理学联系起来进行讨论,例如哈钦森-吉尔福德早衰综合征(一种伴有心血管损伤的早衰疾病)。更多地了解 LINC 复合物的调控和功能将有助于理解细胞核如何参与内皮细胞的力传感以及功能障碍如何导致心血管疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Life at the crossroads: the nuclear LINC complex and vascular mechanotransduction
Vascular endothelial cells line the inner surface of all blood vessels, where they are exposed to polarized mechanical forces throughout their lifespan. Both basal substrate interactions and apical blood flow-induced shear stress regulate blood vessel development, remodeling, and maintenance of vascular homeostasis. Disruption of these interactions leads to dysfunction and vascular pathologies, although how forces are sensed and integrated to affect endothelial cell behaviors is incompletely understood. Recently the endothelial cell nucleus has emerged as a prominent force-transducing organelle that participates in vascular mechanotransduction, via communication to and from cell-cell and cell-matrix junctions. The LINC complex, composed of SUN and nesprin proteins, spans the nuclear membranes and connects the nuclear lamina, the nuclear envelope, and the cytoskeleton. Here we review LINC complex involvement in endothelial cell mechanotransduction, describe unique and overlapping functions of each LINC complex component, and consider emerging evidence that two major SUN proteins, SUN1 and SUN2, orchestrate a complex interplay that extends outward to cell-cell and cell-matrix junctions and inward to interactions within the nucleus and chromatin. We discuss these findings in relation to vascular pathologies such as Hutchinson-Gilford progeria syndrome, a premature aging disorder with cardiovascular impairment. More knowledge of LINC complex regulation and function will help to understand how the nucleus participates in endothelial cell force sensing and how dysfunction leads to cardiovascular disease.
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