Delayed localization of A-type lamins to the rupture sites in Hutchinson–Gilford progeria syndrome

Abstract

The nuclear lamina (NL) lines the inner nuclear membrane (INM) of the nuclear envelope (NE) to maintain nuclear structure in metazoan cells. The major NL components, the nuclear lamins contribute to the protection against NE rupture induced by mechanical stress. Lamin C (LC) but not lamin A (LA) is rapidly diffused from the nucleoplasm to sites of NE rupture induced by laser microirradiation in immortalized mouse embryonic fibroblasts (MEFs). However, the molecular mechanism for differentiating LA from LC with respect to the localization/accumulation at the rupture sites still remains unknown. In this study, we reveal by immunofluorescence, live-cell imaging and fluorescence correlation spectroscopy (FCS) that the CaaX motif, the second cleavage site and the LA-characteristic segment (LACS) regulate the localization of LA to the rupture sites. Our data suggest that Hutchinson–Gilford Progeria syndrome (HGPS) might exhibit the delay in localizing LA to the rupture sites through this mechanism.

The molecular basis of lamin-specific chromatin interactions

“…Consequently, this leads to reduced dynamics of lamin A compared to lamin C, as shown previously 48 . Indeed, the removal of a fragment of lamin A that contains LA 572-588 increases its mobility at the NL 49 .…”