Phosphorylation of lamins determine their structural properties and signaling functions

Abstract

Lamin A/C is part of the nuclear lamina, a meshwork of intermediate filaments underlying the inner nuclear membrane. The lamin network is anchoring a complex set of structural and linker proteins and is either directly or through partner proteins also associated or interacting with a number of signaling protein and transcription factors. During mitosis the nuclear lamina is dissociated by well established phosphorylation- dependent mechanisms. A-type lamins are, however, also phosphorylated during interphase. A recent study identified 20 interphase phosphorylation sites on lamin A/C and explored their functions related to lamin dynamics; movements, localization and solubility. Here we discuss these findings in the light of lamin functions in health and disease.

Keywords: EDMD, Emery-Dreifuss muscular dystrophy; GFP, green fluorescent protein; IFs, intermediate filaments; LAP2α, Lamina-associated polypeptide 2 isoform α; intermediate filaments; lamin A/C; laminopathy; lamins; phosphorylation; signaling.

Figure 1.

Interphase phosphorylation of lamin A/C. The phosphorylation sites identified from interphase HeLa-cells by Kochin et al. The phosphorylation is clustered to the head, the beginning of the tail and the end of the tail. 1A, 1B, 2A and 2B represents the coils of the lamin rod-domain, NLS is the nuclear localization signal.

Figure 2.

Lamin phosphorylation as a regulator of cell signaling. The information that a cell receives from its environment or from within itself is forwarded to the nucleus where it affects the localization and structure of lamin A/C. The physical distribution of lamin A/C can both be affected by phosphorylation and in itself affect the phosphorylation of lamin A/C. The localization, structure, and phosphorylation in turn regulate the functions of lamin A/C and will influence signaling output such as cell movement and mechanosensing.