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.

• Authors: Cristina Capanni, Rosalba Del Coco, Elisabetta Mattioli, Daria Camozzi, Marta Columbaro, Elisa Schena, Luciano Merlini, Stefano Squarzoni, Nadir Mario Maraldi, Giovanna Lattanzi
• Journal: Biology of the cell (Biol Cell) Vol. 101 Issue 9 Pg. 541-54 (Sep 2009) ISSN: 1768-322X [Electronic] England
• PMID: 19323649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lamin Type A
• Membrane Proteins
• Nuclear Proteins
• Protein Precursors
• emerin
• prelamin A

Topics

• Cell Line
• Cells, Cultured
• Fibroblasts (metabolism)
• Humans
• Lamin Type A
• Membrane Proteins (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Protein Binding
• Protein Precursors (genetics, metabolism)
• Protein Processing, Post-Translational
• Protein Transport