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Gangliosides of various types, especially GM1, are known to have a role in some aspects of Ca<jats:sup>2+<\/jats:sup>regulation, operating through a variety of mechanisms that are gradually coming to light. The present study provides evidence for a sodium\u2013calcium exchanger in the nuclear envelope of NG108\u201015 neuroblastoma cells that is potently and specifically activated by GM1. Immunoblot analysis revealed an unusually tight association of GM1 with the exchanger in the nuclear envelope but not with that in the plasma membrane. Exchanger and associated GM1 were located in the inner membrane of the nuclear envelope, suggesting this system could function to transfer Ca<jats:sup>2+<\/jats:sup>between nucleoplasm and the envelope lumen. The GM1\u2010enhanced exchange was blocked by cholera toxin B subunit while C2\u2010ceramide, a recently discovered inhibitor of the exchanger, blocked all transfer. Exchanger activity was significantly elevated in nuclei isolated from cells that were induced to differentiate by KCl + dibutyryl\u2010cAMP, a treatment previously shown to promote up\u2010regulation of nuclear GM1 in conjunction with axonogenesis. Similar enhancement was achieved by addition of exogenous GM1 to nuclei from undifferentiated cells. These results suggest a prominent role for nuclear GM1 in regulation of nuclear Ca<jats:sup>2+<\/jats:sup>homeostasis.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2002.00917.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T07:00:53Z","timestamp":1047452453000},"page":"1185-1195","source":"Crossref","is-referenced-by-count":89,"title":["Potentiation of a sodium\u2013calcium exchanger in the nuclear envelope by nuclear GM1 ganglioside"],"prefix":"10.1111","volume":"81","author":[{"given":"Xin","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gusheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi\u2010Hua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W.","family":"Ledeen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,6,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/367745a0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90105-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.763"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000699"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1523\/JNEUROSCI.14-04-02272.1994","article-title":"Endogenous ganglioside GM1 modulates 1\u2010type calcium channel activity in N18 neuroblastoma cells","volume":"14","author":"Carlson R. 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