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Calcium‐mediated regulation of the Ran gradient and karyopherin nuclear transport receptors.
Author(s) -
Grenet Ashley,
Woodward Stephanie,
Resendes Karen K
Publication year - 2012
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.26.1_supplement.588.1
Subject(s) - karyopherin , ran , nuclear transport , thapsigargin , importin , microbiology and biotechnology , ionomycin , calcium signaling , calcium , endoplasmic reticulum , nucleoporin , trpv6 , sgk1 , chemistry , biology , calcium metabolism , cytoplasm , signal transduction , cell nucleus , intracellular , kinase , organic chemistry
Several cellular stresses, such as UV radiation, heat shock, and oxidative or hyperosmotic stress can cause a disruption of two key regulators of nuclear protein transport, the Ran gradient and karyopherin transport factors. We have demonstrated that cellular stress induced by increasing cellular calcium, either by the introduction of Thapsigargin, an inhibitor of Ca 2 ⁺ uptake into the endoplasmic reticulum, or Ionomycin, which releases calcium from the endoplasmic reticulum, disrupts nuclear transport in HeLa cells. We sought to determine if variation of cellular calcium levels affected nuclear transport through alterations of Ran or karyopherins. We revealed that altering calcium levels leads to an accumulation of Ran in the cytoplasm. Additionally, cells treated with thapsigargin or ionomycin experience relocation of several karyopherins such as Crm1, Importin alpha, Importin beta, and Transportin. Persistent exposure to either drug leads to cellular death. However, the disruption of the Ran gradient can be reversed and rescue is enhanced by the presence of a calcium chelator, BAPTA. These results suggest that alteration of cellular calcium levels, causes the localization of Ran to be disrupted along with that of the nuclear transport factors, suggesting that their is indeed a role for calcium as a regulator in the traditional Ran‐mediated nuclear transport pathways.