Investigating the purpose of prelamin A processing.

Abstract

Lmna yields two major protein products in somatic cells, lamin C and prelamin A. Mature lamin A is produced from prelamin A by four posttranslational processing steps-farnesylation of a carboxyl-terminal cysteine, release of the last three amino acids of the protein, methylation of the farnesylcysteine, and the endoproteolytic release of the carboxyl-terminal 15 amino acids of the protein (including the farnesylcysteine methyl ester). Although the posttranslational processing of prelamin A has been conserved in vertebrate evolution, its physiologic significance remains unclear. Here we review recent studies in which we investigated prelamin A processing with Lmna knock-in mice that produce exclusively prelamin A (Lmna(PLAO)), mature lamin A (Lmna(LAO)) or nonfarnesylated prelamin A (Lmna(nPLAO)). We found that the synthesis of lamin C is dispensable in laboratory mice, that the direct production of mature lamin A (completely bypassing all prelamin A processing) causes no discernable pathology in mice, and that exclusive production of nonfarnesylated prelamin A leads to cardiomyopathy.

• Authors: Brandon Sj Davies, Catherine Coffinier, Shao H Yang, Richard H Barnes 2nd, Hea-Jin Jung, Stephen G Young, Loren G Fong
• Journal: Nucleus (Austin, Tex.) (Nucleus) 2011 Jan-Feb Vol. 2 Issue 1 Pg. 4-9 ISSN: 1949-1042 [Electronic] United States
• PMID: 21647293 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Lamin Type A
• Lamins
• Nuclear Proteins
• Protein Precursors
• prelamin A

Topics

• Animals
• Lamin Type A
• Lamins (deficiency, genetics, metabolism)
• Mice
• Nuclear Proteins (metabolism)
• Progeria (metabolism, pathology)
• Protein Precursors (metabolism)
• Protein Prenylation
• Protein Processing, Post-Translational