ArticleCommunications biology2025
Elevated SUN1 promotes migratory cell polarity defects through mechanically coupling microtubules to the nuclear lamina.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The nucleus as a mechanobiological hub in muscle aging.Nucleus (Austin, Tex.) · 2026Review
- Farnesylated prelamin A induces fibroblast polarity defects in premature aging disorders by inhibiting nesprin-2-SUN2 LINC complex function.Journal of cell science · 2026Article
- Arabidopsis KASH domains are differentially required for distinct LINC complex roles in stomata, roots and pollen.Journal of cell science · 2026Article
- SV40 exploits the Nesprin-2-SUN1-KPNA4 axis for stepwise targeting and entry into the host nucleus to promote infection.PLoS pathogens · 2026Article
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Authors and funding
8 authors.
Funding
Abstract
In migratory fibroblasts, front-rear polarity is defined by the centrosome positioned anterior to a rearward nucleus. To achieve this polarity, actin cables couple to nuclear membrane proteins nesprin-2G and SUN2 and drive the nucleus backward. Aging disrupts this polarity by increasing SUN1, a SUN2 homolog. Here, we investigated the molecular mechanisms behind this disruption and found that the dominant-negative effect of SUN1 and progerin, a lamin A variant, required direct SUN1-lamin A interaction. Microtubule interaction and force transmission through a nesprin, identified as nesprin-2, are crucial for SUN1's effect. We further discovered that stable microtubules are both necessary and sufficient to inhibit cell polarity. Using SUN1-SUN2 chimeric proteins, we demonstrated that the SUN domains determine their roles in cell polarization. Our findings reveal how elevated SUN1 disrupts cell polarity through coupling microtubules and nuclear lamina, emphasizing the impact of altered microtubule stability and nuclear mechanotransduction in polarity defects.
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Registered trials
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