A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells




TekijätStenvall Carl-Gustaf A, Nyström Joel H, Butler-Hallissey Ciarán, Jansson Theresia, Heikkilä Taina R. H, Adam Stephen A, Foisner Roland, Goldman Robert D, Ridge Karen M, Toivola Diana M.

KustantajaAmerican Society for Cell Biology

Julkaisuvuosi2022

JournalMolecular Biology of the Cell

Tietokannassa oleva lehden nimiMolecular biology of the cell

Vuosikerta33

Numero13

ISSN1939-4586

eISSN1939-4586

DOIhttps://doi.org/10.1091/mbc.E20-06-0387

Verkko-osoitehttps://doi.org/10.1091/mbc.E20-06-0387

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/176929630


Tiivistelmä

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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Last updated on 2024-26-11 at 22:21