Emerin—prelamin A interplay in human fibroblasts

Abstract

Background information . Emerin is a nuclear envelope protein that contributes to nuclear architecture, chromatin structure, and gene expression through its interaction with various nuclear proteins. In particular, emerin is molecularly connected with the nuclear lamina, a protein meshwork composed of lamins and lamin‐binding proteins underlying the inner nuclear membrane. Among nuclear lamina components, lamin A is a major emerin partner. Lamin A, encoded by the LMNA gene (lamin A/C gene), is produced as a precursor protein (prelamin A) that is post‐transcriptionally modified at its C‐terminal region where the CaaX motif triggers a sequence of modifications, including farnesylation, carboxymethylation, and proteolytic cleavage by ZMPSTE 24 (zinc metalloproteinase Ste24) metalloproteinase. Impairment of the lamin A maturation pathway causing lamin A precursor accumulation is linked to the development of rare diseases such as familial partial lipodystrophy, MADA (mandibuloacral dysplasia), the Werner syndrome, Hutchinson—Gilford progeria syndrome and RD (restrictive dermopathy). Results . In the present study, we show that emerin and different prelamin A forms influence each other's localization. We show that the accumulation of non‐farnesylated as well as farnesylated carboxymethylated lamin A precursors in human fibroblasts modifies emerin localization. On the contrary, emerin absence at the inner nuclear membrane leads to unprocessed (non‐farnesylated) prelamin A aberrant localization only. Moreover, we observe that the restoration of emerin expression in emerin‐null cells induces the recovery of non‐farnesylated prelamin A localization. Conclusion . These results indicate that emerin—prelamin A interplay influences nuclear organization. This finding may be relevant to the understanding of laminopathies.