Concentric organization of A- and B-type lamins predicts their distinct roles in the spatial organization and stability of the nuclear lamina

Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4307-4315. doi: 10.1073/pnas.1810070116. Epub 2019 Feb 14.


The nuclear lamina is an intermediate filament meshwork adjacent to the inner nuclear membrane (INM) that plays a critical role in maintaining nuclear shape and regulating gene expression through chromatin interactions. Studies have demonstrated that A- and B-type lamins, the filamentous proteins that make up the nuclear lamina, form independent but interacting networks. However, whether these lamin subtypes exhibit a distinct spatial organization or whether their organization has any functional consequences is unknown. Using stochastic optical reconstruction microscopy (STORM) our studies reveal that lamin B1 and lamin A/C form concentric but overlapping networks, with lamin B1 forming the outer concentric ring located adjacent to the INM. The more peripheral localization of lamin B1 is mediated by its carboxyl-terminal farnesyl group. Lamin B1 localization is also curvature- and strain-dependent, while the localization of lamin A/C is not. We also show that lamin B1's outer-facing localization stabilizes nuclear shape by restraining outward protrusions of the lamin A/C network. These two findings, that lamin B1 forms an outer concentric ring and that its localization is energy-dependent, are significant as they suggest a distinct model for the nuclear lamina-one that is able to predict its behavior and clarifies the distinct roles of individual nuclear lamin proteins and the consequences of their perturbation.

Keywords: bleb; curvature; lamin; meshwork; nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Nucleus / metabolism
  • HeLa Cells
  • Humans
  • Lamin Type A* / chemistry
  • Lamin Type A* / genetics
  • Lamin Type A* / metabolism
  • Lamin Type B* / chemistry
  • Lamin Type B* / genetics
  • Lamin Type B* / metabolism
  • Microscopy
  • Nuclear Envelope / metabolism
  • Nuclear Lamina* / metabolism


  • lamin B1
  • Lamin Type A
  • Lamin Type B