Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: Altered intermolecular interaction with emerin and implications for gene transcription

Cristina Capanni, Vittoria Cenni, Elisabetta Mattioli, Patrizia Sabatelli, Andrea Ognibene, Marta Columbaro, Veena K. Parnaik, Manfred Wehnert, Nadir M. Maraldi, Stefano Squarzoni, Giovanna Lattanzi

Research output: Contribution to journalArticle

Abstract

Familial partial lipodystrophy is an autosomal dominant disease caused by mutations of the LMNA gene encoding alternatively spliced lamins A and C. Abnormal distribution of body fat and insulin resistance characterize the clinical phenotype. In this study, we analyzed primary fibroblast cultures from a patient carrying an R482L lamin A/C mutation by a morphological and biochemical approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates mostly localized close to the nuclear lamina. These aggregates were not bound to either DNA-containing structures or RNA splicing intranuclear compartments. In addition, emerin did not colocalize with nuclear lamin A/C aggregates. Interestingly, emerin failed to interact with lamin A in R482L mutated fibroblasts in vivo, while the interaction with lamin C was preserved in vitro, as determined by coimmunoprecipitation experiments. The presence of lamin A/C nuclear aggregates was restricted to actively transcribing cells, and it was increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C nuclear aggregates, a reduced incorporation of bromouridine was observed, demonstrating that mutated lamin A/C in FPLD cells interferes with RNA transcription.

Original languageEnglish
Pages (from-to)122-134
Number of pages13
JournalExperimental Cell Research
Volume291
Issue number1
DOIs
Publication statusPublished - Nov 15 2003

Keywords

  • Chromatin disorganization
  • Familial partial lipodystrophy
  • Gene transcription
  • Intranuclear lamin A/C speckles
  • Lamin A/C
  • Lamin-emerin interaction

ASJC Scopus subject areas

  • Cell Biology

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