Publications · PNAS 2024 · First author

Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina

Revealed large, irregular openings in the progerin meshwork and showed that higher lamin B1 expression can normalize its structure and reduce nuclear rupture.

The question

Progerin makes the nuclear membrane rupture and bleb, but how does it change the structure of the nuclear lamina itself?

What we found

• High-resolution microscopy showed that lamin A and lamin B1 normally form independent meshworks with small, evenly spaced openings (about 0.085 µm).
• Progerin forms an irregular meshwork with clusters of large openings, up to 1.4 µm.
• Progerin also disrupts the normal lamin B1 meshwork, a dominant-negative effect, and these abnormal meshworks go hand in hand with nuclear ruptures and blebs.
• Raising lamin B1 levels restored the meshwork's structure and markedly reduced ruptures and blebs.

Why it matters

It shows how progerin weakens the nucleus at the level of the lamin meshwork, and that boosting lamin B1 can reverse the damage in cells.

Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina. PNAS (2024). doi:10.1073/pnas.2406946121