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Sodium–Calcium Exchangers in the Nucleus
Author(s) -
LEDEEN ROBERT W.,
WU GUSHENG
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.057
Subject(s) - nucleoplasm , chemistry , cytoplasm , calcium , microbiology and biotechnology , nucleus , homeostasis , nuclear lamina , sodium calcium exchanger , nuclear membrane , biophysics , biochemistry , biology , nuclear protein , transcription factor , organic chemistry , gene , nucleolus
Whereas sodium–calcium exchangers (NCXs) have long been recognized as plasma membrane constituents that serve to maintain homeostatic concentrations of Ca 2+ in the cytoplasm, they were recently shown to also occur in the nuclear envelope (NE) of neural and other cells where they function to regulate nuclear Ca 2+ . A unique feature of NCXs in the NE is their high‐affinity binding to GM1 ganglioside, this association being required for optimal exchanger activity. The NCX–GM1 complex occurs in the inner membrane of the NE and transfers Ca 2+ from the nucleoplasm to the NE lumen. In neuronal cells, nuclear GM1 levels are low prior to differentiation but increase rapidly as axonal outgrowth progresses. Cells from genetically altered mice lacking GM1 have limited ability to regulate nuclear Ca 2+ , and the mice themselves showed similar deficit as seen in their high susceptibility to kainite‐induced seizures. These are attenuated by LIGA‐20, a derivative of GM1 that enters the nuclear membrane and restores nuclear NCX activity to normal level.