The stability of the nuclear lamina polymer changes with the composition of lamin subtypes according to their individual binding strengths.
The nuclear lamina, which provides a structural scaffolding for the nuclear envelope, consists largely of a polymer of the intermediate filament lamin proteins. Although different cell types contain distinctive relative amounts of the major lamin subtypes (A, C, B1, and B2), the functions of this variation are not understood. We have investigated the possibility that subtype variation affects lamina stability. We find that homotypic and heterotypic binding interactions of lamin B2 are substantially less resistant to chemical dissociation in vitro than those between the other lamin subtypes, whereas lamin A interactions are the most stable. Surprisingly, removal of the central four-fifths of the rod domain did not substantially weaken the interactions of lamins A and B2, suggesting that other regions also strongly contribute to their binding interactions. In contrast, this rod deletion strongly destabilizes the binding interactions of lamins B1 and C. Consistent with the binding studies, lamins are more readily solubilized by chemical extraction from cells enriched for lamin B2 than from cells enriched for lamin A. This suggests that the distinctive ensemble of heterotypic lamin interactions in a particular cell type affects the stability of the lamin polymer, and, correspondingly, could be relevant to tissue-specific properties of the lamina including its involvement in disease.
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Eric C
EC
Schirmer
Larry
L
Gerace
D002460:Cell Line; D003902:Detergents / Q000494:pharmacology; D017353:Gene Deletion; D018922:HL-60 Cells; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry*; D034921:Lamin Type B / Q000737:chemistry*; D008957:Models, Genetic; D034881:Nuclear Lamina / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014508:Urea / Q000494:pharmacology
D003902:Detergents; D034904:Lamin Type A; D034921:Lamin Type B; D011108:Polymers; C440308:lamin C; D014508:Urea