Structural and physiological phenotypes of disease-linked lamin mutations in C. elegans

Erin M. Bank, Kfir Ben-Harush, Naomi Feinstein, Ohad Medalia, Yosef Gruenbaum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The nuclear lamina is a major structural element of the nucleus and is predominately composed of the intermediate filament lamin proteins. Missense mutations in the human lamins A/C cause a family of laminopathic diseases, with no known mechanistic link between the position of the mutation and the resulting disease phenotypes. The. Caenorhabditis elegans lamin (Ce-lamin) is structurally and functionally homologous to human lamins, and recent advances have allowed detailed structural analysis of Ce-lamin filaments both. in vitro and. in vivo. Here, we studied the effect of laminopathic mutations on Ce-lamin filament assembly. in vitro and the corresponding physiological phenotypes in animals. We focused on three disease-linked mutations, Q159K, T164P, and L535P, which have previously been shown to affect lamin structure and nuclear localization. Mutations prevented the proper assembly of Ce-lamin into filament and/or paracrystalline arrays. Disease-like phenotypes were observed in strains expressing low levels of these mutant lamins, including decreased fertility and motility coincident with muscle lesions. In addition, the Q159K- and T164P-expressing strains showed a reduced lifespan. Thus, different disease-linked mutations in Ce-lamin exhibit major effects. in vivo and. in vitro. Using. C. elegans as a model system, a comprehensive analysis of the effects of specific lamin mutations from the level of. in vitro filament assembly to the physiology of the organism will help uncover the mechanistic differences between these different lamin mutations.

Original languageEnglish
Pages (from-to)106-112
Number of pages7
JournalJournal of Structural Biology
Volume177
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Caenorhabditis elegans
  • EDMD
  • HGPS
  • Laminopathic diseases
  • Nuclear lamina

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