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This is consistent with localization of the NCX\/GM1 complex in the inner membrane of the NE. NCXs of the plasma membrane, in contrast, appear to bind GM1 much less avidly. This is believed due to different isoforms of NCX in the two membranes, and a difference in topology of NCX relative to GM1. A cytoprotective function for nuclear NCX\/GM1 was suggested in the observation that cultured neurons from mice lacking GM1 (GM2\/GD2 synthase knockout) were vulnerable to Ca<jats:sup>2+<\/jats:sup>\u2010induced apoptosis. These neurons in culture were rescued to some extent by GM1 but more effectively by LIGA\u201020, a membrane\u2010permeant derivative of GM1 that entered the NE. Further indication came from a study of the mutant mice, which were highly susceptible to kainate\u2010induced seizures and could be rescued by LIGA\u201020. This correlated with the ability of LIGA\u201020 to cross the blood\u2013brain barrier, enter brain cells, insert into the NE, and potentiate nuclear NCX.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04722.x","type":"journal-article","created":{"date-parts":[[2007,11,6]],"date-time":"2007-11-06T11:51:44Z","timestamp":1194349904000},"page":"126-134","source":"Crossref","is-referenced-by-count":38,"title":["GM1 in the nuclear envelope regulates nuclear calcium through association with a nuclear sodium\u2010calcium exchanger"],"prefix":"10.1111","volume":"103","author":[{"given":"Robert","family":"Ledeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gusheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,11,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(81)90411-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.763"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8446902"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00448-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10333"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0155-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1016\/S0021-9258(18)53608-5","article-title":"Identification and purification of a calcium\u2010binding protein in hepatic nuclear membranes","volume":"268","author":"Gilchrist J. 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