Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins

Naama Wiesel, Anna Mattout, Shai Melcer, Naomi Melamed-Book, Harald Herrmann, Ohad Medalia, Ueli Aebi, Yosef Gruenbaum

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


Lamins are nuclear intermediate filament proteins and the major building blocks of the nuclear lamina. Besides providing nuclear shape and mechanical stability, lamins are required for chromatin organization, transcription regulation, DNA replication, nuclear assembly, nuclear positioning, and apoptosis. Mutations in human lamins cause many different heritable diseases, affecting various tissues and causing early aging. Although many of these mutations result in nuclear deformation, their effects on lamin filament assembly are unknown. Caenorhabditis elegans has a single evolutionarily conserved lamin protein, which can form stable 10-nmthick filaments in vitro. To gain insight into the molecular basis of lamin filament assembly and the effects of laminopathic mutations on this process, we investigated mutations in conserved residues of the rod and tail domains that are known to cause various laminopathies in human. We show that 8 of 14 mutant lamins present WT-like assembly into filaments or paracrystals, whereas 6 mutants show assembly defects. Correspondingly, expressing these mutants in transgenic animals shows abnormal distribution of Ce-lamin, abnormal nuclear shape or change in lamin mobility. These findings help in understanding the role of individual residues and domains in laminopathy pathology and, eventually, promote the development of therapeutic interventions.

Original languageEnglish
Pages (from-to)180-185
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - 8 Jan 2008


  • Filament assembly
  • Laminopathic diseases
  • Nuclear envelope

ASJC Scopus subject areas

  • General


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