拉明
普莱克汀
生物
核板
细胞生物学
核质
中间灯丝
角蛋白
角蛋白8
细胞质
核蛋白
分子生物学
细胞
核心
细胞骨架
生物化学
遗传学
转录因子
核仁
基因
作者
Carl-Gustaf A. Stenvall,Joel H. Nyström,Ciarán Butler-Hallissey,Theresia Jansson,Taina Heikkilä,Stephen A. Adam,Roland Foisner,Robert D. Goldman,Karen M. Ridge,Diana M. Toivola
标识
DOI:10.1091/mbc.e20-06-0387
摘要
Keratin intermediate filaments convey mechanical stability and protection against stress to epithelial cells. Keratins are essential for colon health, as seen in keratin 8 knockout (K8-/-) mice exhibiting a colitis phenotype. We hypothesized that keratins support the nuclear envelope and lamina in colonocytes. K8-/- colonocytes in vivo exhibit significantly decreased levels of lamins A/C, B1, and B2 in a colon-specific and cell-intrinsic manner. CRISPR/Cas9- or siRNA-mediated K8 knockdown in Caco-2 cells similarly decreased lamin levels, which recovered after reexpression of K8 following siRNA treatment. Nuclear area was not decreased, and roundness was only marginally increased in cells without K8. Down-regulation of K8 in adult K8flox/flox;Villin-CreERt2 mice following tamoxifen administration significantly decreased lamin levels at day 4 when K8 levels had reduced to 40%. K8 loss also led to reduced levels of plectin, LINC complex, and lamin-associated proteins. While keratins were not seen in the nucleoplasm without or with leptomycin B treatment, keratins were found intimately located at the nuclear envelope and complexed with SUN2 and lamin A. Furthermore, K8 loss in Caco-2 cells compromised nuclear membrane integrity basally and after shear stress. In conclusion, colonocyte K8 helps maintain nuclear envelope and lamina composition and contributes to nuclear integrity.
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