Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress

S Angori, Cristina Capanni, G. P. Faulkner-Valle, C. Bean, Giusppe Boriani, Giovanna Lattanzi, Vittoria Cenni

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND:
Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear.
METHODS:
Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS) release and cell viability.
RESULTS:
Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart.
CONCLUSIONS:
For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.
Original languageEnglish
Pages (from-to)169-184
Number of pages16
JournalCellular Physiology and Biochemistry
Volume42
Issue number1
DOIs
Publication statusPublished - May 25 2017

Fingerprint

Emery-Dreifuss Muscular Dystrophy
Lamin Type A
Heat-Shock Proteins
Oxidative Stress
Muscle Cells
Skeletal Muscle Fibers
Immunoprecipitation
Genes
Fluorescent Antibody Technique
Reactive Oxygen Species
Cell Survival
Cell Line

Keywords

  • Ankrd2 (Ankyrin Repeat Domain 2)
  • EDMD2 (Emery-Dreifuss Muscular Dystrophy 2)
  • Human muscle cells
  • Lamin A/C
  • Oxidative stress
  • Prelamin A

Cite this

Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress. / Angori, S; Capanni, Cristina; Faulkner-Valle, G. P.; Bean, C.; Boriani, Giusppe; Lattanzi, Giovanna; Cenni, Vittoria.

In: Cellular Physiology and Biochemistry, Vol. 42, No. 1, 25.05.2017, p. 169-184.

Research output: Contribution to journalArticle

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title = "Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress",
abstract = "BACKGROUND:Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear.METHODS:Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS) release and cell viability.RESULTS:Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart.CONCLUSIONS:For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.",
keywords = "Ankrd2 (Ankyrin Repeat Domain 2), EDMD2 (Emery-Dreifuss Muscular Dystrophy 2), Human muscle cells, Lamin A/C, Oxidative stress, Prelamin A",
author = "S Angori and Cristina Capanni and Faulkner-Valle, {G. P.} and C. Bean and Giusppe Boriani and Giovanna Lattanzi and Vittoria Cenni",
year = "2017",
month = "5",
day = "25",
doi = "10.1159/000477309",
language = "English",
volume = "42",
pages = "169--184",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
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number = "1",

}

TY - JOUR

T1 - Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress

AU - Angori, S

AU - Capanni, Cristina

AU - Faulkner-Valle, G. P.

AU - Bean, C.

AU - Boriani, Giusppe

AU - Lattanzi, Giovanna

AU - Cenni, Vittoria

PY - 2017/5/25

Y1 - 2017/5/25

N2 - BACKGROUND:Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear.METHODS:Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS) release and cell viability.RESULTS:Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart.CONCLUSIONS:For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.

AB - BACKGROUND:Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear.METHODS:Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS) release and cell viability.RESULTS:Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart.CONCLUSIONS:For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.

KW - Ankrd2 (Ankyrin Repeat Domain 2)

KW - EDMD2 (Emery-Dreifuss Muscular Dystrophy 2)

KW - Human muscle cells

KW - Lamin A/C

KW - Oxidative stress

KW - Prelamin A

U2 - 10.1159/000477309

DO - 10.1159/000477309

M3 - Article

VL - 42

SP - 169

EP - 184

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 1

ER -