Abstract
In mammalian cell nuclei, the nuclear lamina (NL) underlies the nuclear envelope (NE) to maintain nuclear structure. The nuclear lamins, the major structural components of the NL, are involved in the protection against NE rupture induced by mechanical stress. However, the specific role of the lamins in repair of NE ruptures has not been fully determined. Our analyses using immunofluorescence and live-cell imaging revealed that the nucleoplasmic pool of lamin C rapidly accumulated at sites of NE rupture induced by laser microirradiation in mouse embryonic fibroblasts. The accumulation of lamin C at the rupture sites required both the immunoglobulin-like fold domain that binds to barrier-to-autointegration factor (BAF) and a nuclear localization signal. The accumulation of nuclear BAF and cytoplasmic cyclic GMP-AMP synthase (cGAS) at the rupture sites was in part dependent on lamin A/C. These results suggest that nucleoplasmic lamin C, BAF, and cGAS concertedly accumulate at sites of NE rupture for rapid repair.
| Original language | English (US) |
|---|---|
| Article number | e202201024 |
| Journal | Journal of Cell Biology |
| Volume | 221 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 5 2022 |
Funding
We thank Open Facility Center (OFC) and Open Research Fa-cilities for Life Science and Technology (ORFLT) of Tokyo Institute of Technology for nucleotide sequencing and technical assistance, especially Sachiko Muto for image analysis. We also thank all members of the Kimura lab at Tokyo Institute of Technology, especially Harumi Ueno for constructing psfCherry-N2, Misako Tanaka and Akito Ohi for constructing pLKO.2-hygro-shScramble, and Arata Komatsubara for image analysis. This work was supported by JSPS KAKENHI grant nos. JP20KK0158 (to T. Shimi, Y. Kono, and H. Kimura), JP20K06617 (to T. Shimi), and JP18H05527 and JP21H04764 (to H. Kimura). Y. Kono is an academy scholar at the Specialized Academy for Cell Science (Ohsumi-juku) of the Tokyo Tech Organization for Fundamental Research (OFR). This work was supported by JSPS KAKENHI grant nos. JP20KK0158 (to T. Shimi, Y. Kono, and H. Kimura), JP20K06617 (to T. Shimi), and JP18H05527 and JP21H04764 (to H. Kimura). Y. Kono is an academy scholar at the Specialized Academy for Cell Science (Ohsumi-juku) of the Tokyo Tech Organization for Fundamental Research (OFR). The authors declare no competing financial interests.
ASJC Scopus subject areas
- Cell Biology