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Disease‐causing mutations of Lamin A lead to loss of calcium homeostasis in the endo/sarcoplasmic reticulum
Author(s) -
Chi YaHui,
Lin WenHsin,
Wang WanPing,
Kao ChengHeng,
Wang JingYa,
Teng YuanChi,
Tsai TingFen
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.533.110
Subject(s) - lmna , lamin , serca , endoplasmic reticulum , microbiology and biotechnology , skeletal muscle , biology , unfolded protein response , nuclear lamina , emerin , genetics , endocrinology , gene , transcription factor , nuclear protein , biochemistry , atpase , enzyme , nucleus
Mutations in nuclear lamin A are responsible for several rare human diseases, including the Emery‐Dreifuss muscular dystrophy (AD‐EDMD) and the Hutchinson‐Gilford progeria syndrome (HGPS). Here we show that structure of the endo/sarcoplasmic reticulum (ER/SR) is disrupted in HGPS cells and skeletal muscle of Lmna mutant mice. However, only a slight increase in ER stress‐associated genes was observed. Microarray analysis revealed that expression of several calcium signaling‐associated genes were disturbed in the skeletal muscle of Lmna mutant mice compare to the wild type cohorts. Sacrolipin ( Sln ), a SERCA activity modulator, is highly expressed and serves as a protective factor for the lifespan of Lmna −/− mice. In a myoblast cellular system inducibly expressing progerin to model HGPS, we found increased store operated Ca 2+ entry (SOCE) and colocalization of Stim1 and Orai1. These findings suggest that the nuclear lamin A is structurally and functionally connected to the robustness of ER/SR for calcium homeostasis. Support or Funding Information This work was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 105‐2633‐B‐400‐001 and MOST 105‐2320‐B‐400‐020). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .