Do lamin A and lamin C have unique roles?

Abstract

The A-type lamins, lamin A and lamin C, generated from a single gene, LMNA, are major structural components of the nuclear lamina. The two alternative splice products have mostly been studied together because they have been considered to be interchangeable. However, several lines of evidence indicate that in spite of being generated from the same gene and having high similarities in their primary sequences, the two isoforms are not equivalent in different biological aspects in both health and disease. The key question is whether they have both overlapping and unique functions and whether they are distinctly regulated. Based on the so far available experimental evidence, lamin A appears to be the most regulated A-type isoform during development, aging, and disease which indicates that lamin A is implicated in many different biological aspects and may have a greater repertoire of specialized functions than lamin C. The aim of this review is to point out differences between the two major LMNA splice variants and the consequences of these differences on their functions. This may guide further research and be of prime importance for the understanding of the pathogenesis of LMNA mutations.

The effect of the lamin A and its mutants on nuclear structure, cell proliferation, protein stability, and mobility in embryonic cells

“…Two LMNA spliced forms (lamin C and lamin A ∆50) even seem to have opposite functions in the context of energy metabolism (Lopez-Mejia et al 2014). It is known that lamins A and C have different expression patterns and binding properties, and it was proposed that the imbalance between those spliced forms can result in pathogenesis (Al-Saaidi and Bross 2015). As observed in our study, lamin C redistribution may suggest the mechanism of this disturbance.…”

“…Although they share many functions, they have different expression patterns, regulatory mechanisms, or assembly properties in different tissues (Al-Saaidi and Bross 2015). The targeting of lamin C and some other proteins (e.g., emerin) to the NE depends on lamin A localization (Pugh et al 1997; Vaughan et al 2001), but it is not clear how lamin mutations influence this process.…”

Speeding up the clock: The past, present and future of progeria

“…B-type lamins, which include lamins B1, B2 and B3, are encoded by the LMNB1 and LMNB2 genes (Gruenbaum et al 2005). Lamins A and C have generally been believed to display functional redundancy, although several lines of evidence indicate that these proteins may have unique biological roles in cell division, embryonic development, and aging (Al-Saaidi & Bross 2015). Lamins have multiple functions and play critical roles in DNA replication and transcription, cell division, and in providing integrity to the chromatin and nuclear membrane of various cell types (Hutchison 2002;Dechat et al 2008).…”

The clinical outcome of LMNA missense mutations can be associated with the amount of mutated protein in the nuclear envelope

“…Lamin A and lamin C proteins constitute the main structural proteins of the inner nuclear envelope. Both isoforms are encoded by the LMNA gene, and are formed after alternative splicing . They are expressed in almost all differentiated tissues, including the myocardium and fibroblasts.…”

“…They are expressed in almost all differentiated tissues, including the myocardium and fibroblasts. In addition to their structural and supportive function of the nucleus, these proteins are believed to influence regulation of gene expression through an interaction with transcription factors, DNA, and chromatin . It has been suggested that haploinsufficiency is the disease mechanism in patients carrying truncating LMNA mutations, while LMNA missense mutations have been proposed to act through a dominant negative pathway .…”