Prelamin A aggregates were found to colocalize with SUN1-labeled nuclear invaginations.
The localization of the mutant protein at the nuclear envelope was similar to that of wild type, although some p.R435C lamin A aggregates were observed (not shown).
These prelamin A aggregates likely represent nuclear lamina invaginations, as suggested by previous studies (Filesi et al. 2005; Lattanzi et al. 2007; Mattioli et al. 2008).
Cells expressing progerin or elevated levels of wild-type prelamin A show abnormal lamin A aggregates in the nucleus, which are also observed in cells from normal old-age individuals but absent in cells from young-age individuals [ 11].
However, complete rescue was not achievable as indicated by the persistence of co-localization with prelamin A aggregates for both SUN2 and SUN1 in control, mevinolin and mevinolin plus trichostatin A treatment conditions.
This has been previously demonstrated in MADA fibroblasts, in which prelamin A aggregates resulted in a reduced availability of free SREBP1, thus affecting the expression of genes involved in adipogenic differentiation (Capanni et al. 2005).
