Altering lamina assembly reveals lamina-dependent and -independent functions for A-type lamins

Monika Zwerger, Heidi Roschitzki-Voser, Reto Zbinden, Celine Denais, Harald Herrmann, Jan Lammerding, Markus G. Grütter, Ohad Medalia

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Lamins are intermediate filament proteins that form a fibrous meshwork, called the nuclear lamina, between the inner nuclear membrane and peripheral heterochromatin of metazoan cells. The assembly and incorporation of lamin A/C into the lamina, as well as their various functions, are still not well understood. Here, we employed designed ankyrin repeat proteins (DARPins) as new experimental tools for lamin research. We screened for DARPins that specifically bound to lamin A/C, and interfered with lamin assembly in vitro and with incorporation of lamin A/C into the native lamina in living cells. The selected DARPins inhibited lamin assembly and delocalized A-type lamins to the nucleoplasm without modifying lamin expression levels or the amino acid sequence. Using these lamin binders, we demonstrate the importance of proper integration of lamin A/C into the lamina for nuclear mechanical properties and nuclear envelope integrity. Finally, our study provides evidence for cell-type-specific differences in lamin functions.

Original languageEnglish
Pages (from-to)3607-3620
Number of pages14
JournalJournal of Cell Science
Volume128
Issue number19
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Assembly
  • DARPins
  • Lamina
  • Lamins
  • Nuclear envelope
  • Nucleus

ASJC Scopus subject areas

  • Cell Biology

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