Role of A-type lamins in signaling, transcription, and chromatin organization

Abstract

A-type lamins (lamins A and C), encoded by the LMNA gene, are major protein constituents of the mammalian nuclear lamina, a complex structure that acts as a scaffold for protein complexes that regulate nuclear structure and functions. Interest in these proteins has increased in recent years with the discovery that LMNA mutations cause a variety of human diseases termed laminopathies, including progeroid syndromes and disorders that primarily affect striated muscle, adipose, bone, and neuronal tissues. In this review, we discuss recent research supporting the concept that lamin A/C and associated nuclear envelope proteins regulate gene expression in health and disease through interplay with signal transduction pathways, transcription factors, and chromatin-associated proteins.

Structural dynamics of the cell nucleus

“…Released c-Fos, in turn, can form dimeric complexes with c-Jun and thereby activate AP-1-dependent gene transcription in the nucleoplasm. 16,17 Thus, deep infoldings may reflect structural remodeling of the cell nucleus due to increased transcriptional activity. At the same time this form of plasticity provides the basis for enhanced and refined nuclear calcium signaling (Fig.…”

“…Second, A-type lamins, which are major components of the nuclear lamina-a protein network controlling nuclear shape, have also been implicated in the regulation of gene transcription and chromatin organization. 16 Pre-existing c-Fos can be sequestered at the nuclear envelope by lamin A/C 17 and their direct phosphorylation by ERK1/2 liberates c-Fos from the nuclear envelope. Released c-Fos, in turn, can form dimeric complexes with c-Jun and thereby activate AP-1-dependent gene transcription in the nucleoplasm.…”

The Nuclear Envelope: An Intriguing Focal Point for Neurogenetic Disease

“…Abnormal nuclear positioning, which can potentially increase susceptibility to damage by mechanical force, also results from pathogenic defects in A-type lamins and emerin [64,65]. An alternative to the "mechanical stress" hypothesis is the notion that alterations in the nuclear envelope cause pathogenic changes in gene expression that are tissue-specific [66]. These possibilities are not mutually exclusive, as mechanical forces on the nuclear membrane are well documented to alter gene expression and these concepts are the focus of current research [67].…”

Dynamics of the Plant Nuclear Envelope and Nuclear Pore

“…Lamins mediate the attachment of chromatin to the NE during interphase and chromatin detachment during mitosis (Gant and Wilson, 1997;Dechat et al, 2010). Lamin mutations cause a variety of human diseases that are collectively termed laminopathies (Andrés and González, 2009). Lamins have not been found outside the metazoan lineage; however, early electron microscopy and immunohistochemistry suggested a nuclear lamina and lamin-like proteins in plants ( Galcheva-Gargova and Stateva, 1988;Li and Roux, 1992;McNulty and Saunders, 1992;Mínguez and Moreno Díaz de la Espina, 1993).…”