Functions and dysfunctions of the nuclear lamin Ig-fold domain in nuclear assembly, growth, and Emery-Dreifuss muscular dystrophy

Dale K. Shumaker, Reynold I. Lopez-Soler, Stephen A. Adam, Harald Herrmann, Robert D. Moir, Timothy P. Spann, Robert D. Goldman*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The non-α-helical C terminus of Xenopus lamin B3 (LB3T) inhibits the polymerization of lamin B3 in vitro and prevents the assembly of nuclei in Xenopus egg interphase extracts. To more precisely define the functions of LB3T in nuclear assembly, we have expressed subdomains of LB3T and determined their effects on nuclear assembly in Xenopus extracts. The results demonstrate that the Ig-fold motif (LB3T-Ig) is sufficient to inhibit lamin polymerization in vitro. Addition of the LB3T-Ig to egg extracts before the introduction of chromatin prevents chromatin decondensation and the assembly of the lamina, membranes, and pore complexes comprising the nuclear envelope. When added to assembled nuclei, LB3T-Ig prevents the further incorporation of lamin B3 into the endogenous lamina and blocks nuclear growth. The introduction of a point mutation in LB3T-Ig (R454W; LB3T-IgRW), known to cause Emery-Dreifuss muscular dystrophy when present in lamin A, does not inhibit lamin polymerization, chromatin decondensation, or nuclear assembly and growth. These results shed light on the specific alterations in lamin functions attributable to a known muscular dystrophy mutation and provide an experimental framework for revealing the effects of other mutations causing a wide range of laminopathies.

Original languageEnglish (US)
Pages (from-to)15494-15499
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number43
DOIs
StatePublished - Oct 25 2005

Keywords

  • Intermediate filaments
  • Laminopathies
  • Nuclear envelope

ASJC Scopus subject areas

  • General

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