PMID- 34685547 OWN - NLM STAT- MEDLINE DCOM- 20220105 LR - 20220105 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 10 DP - 2021 Sep 28 TI - Zonula occludens 2 and Cell-Cell Contacts Are Required for Normal Nuclear Shape in Epithelia. LID - 10.3390/cells10102568 [doi] LID - 2568 AB - MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and instead become resistant to UV-induced senescence. The irregular nuclear shape is also observed in isolated cells and in those without TJs, due to the lack of extracellular calcium. The aberrant nuclear shape of ZO-2 KD cells is not accompanied by a reduced expression of lamins A/C and B and lamin B receptors. Instead, it involves a decrease in constitutive and facultative heterochromatin, and microtubule instability that is restored with docetaxel. ZO-2 KD cells over-express SUN-1 that crosses the inner nuclear membrane and connects the nucleoskeleton of lamin A to nesprins, which traverse the outer nuclear membrane. Nesprins-3 and -4 that indirectly bind on their cytoplasmic face to vimentin and microtubules, respectively, are also over-expressed in ZO-2 KD cells, whereas vimentin is depleted. SUN-1 and lamin B1 co-immunoprecipitate with ZO-2, and SUN-1 associates to ZO-2 in a pull-down assay. Our results suggest that ZO-2 forms a complex with SUN-1 and lamin B1 at the inner nuclear membrane, and that ZO-2 and cell-cell contacts are required for a normal nuclear shape. FAU - Hernandez-Guzman, Christian AU - Hernandez-Guzman C AUID- ORCID: 0000-0003-4372-2073 AD - Center for Research and Advanced Studies (Cinvestav), Department of Physiology, Biophysics and Neuroscience, Ave IPN 2508, Mexico City 07360, Mexico. FAU - Gallego-Gutierrez, Helios AU - Gallego-Gutierrez H AUID- ORCID: 0000-0003-0369-9083 AD - Center for Research and Advanced Studies (Cinvestav), Department of Physiology, Biophysics and Neuroscience, Ave IPN 2508, Mexico City 07360, Mexico. FAU - Chavez-Munguia, Bibiana AU - Chavez-Munguia B AD - Center for Research and Advanced Studies (Cinvestav), Department of Infectomics and Molecular Pathogenesis, Ave IPN 2508, Mexico City 07360, Mexico. FAU - Martin-Tapia, Dolores AU - Martin-Tapia D AD - Center for Research and Advanced Studies (Cinvestav), Department of Physiology, Biophysics and Neuroscience, Ave IPN 2508, Mexico City 07360, Mexico. FAU - Gonzalez-Mariscal, Lorenza AU - Gonzalez-Mariscal L AD - Center for Research and Advanced Studies (Cinvestav), Department of Physiology, Biophysics and Neuroscience, Ave IPN 2508, Mexico City 07360, Mexico. LA - eng GR - FIDSC2018/33/SEP-Cinvestav/ GR - FORDECYT-PRONACES-140644/Consejo Nacional de Ciencia y Tecnologia/ GR - 407499/Consejo Nacional de Ciencia y Tecnologia/ GR - 282075/Consejo Nacional de Ciencia y Tecnologia/ GR - 2018AD0009-11/Consejo Mexiquense de Ciencia y Tecnologia/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210928 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Zonula Occludens-2 Protein) SB - IM MH - Cell Communication/*immunology MH - Epithelium/*metabolism MH - Humans MH - Transfection MH - Zonula Occludens-2 Protein/*metabolism PMC - PMC8534263 OTO - NOTNLM OT - LINC OT - SUN-1 OT - ZO-2 OT - nuclear shape OT - senescence OT - vimentin COIS- The authors declare no conflict of interest. EDAT- 2021/10/24 06:00 MHDA- 2022/01/06 06:00 PMCR- 2021/09/28 CRDT- 2021/10/23 01:22 PHST- 2021/08/20 00:00 [received] PHST- 2021/09/04 00:00 [revised] PHST- 2021/09/06 00:00 [accepted] PHST- 2021/10/23 01:22 [entrez] PHST- 2021/10/24 06:00 [pubmed] PHST- 2022/01/06 06:00 [medline] PHST- 2021/09/28 00:00 [pmc-release] AID - cells10102568 [pii] AID - cells-10-02568 [pii] AID - 10.3390/cells10102568 [doi] PST - epublish SO - Cells. 2021 Sep 28;10(10):2568. doi: 10.3390/cells10102568.