{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:56:37Z","timestamp":1792652197907,"version":"4.5.0"},"reference-count":77,"publisher":"American Society for Cell Biology (ASCB)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:p>Assembly of a eukaryotic nucleus involves three distinct events: membrane recruitment, fusion to form a double nuclear membrane, and nuclear pore complex (NPC) assembly. We report that importin \u03b2 negatively regulates two of these events, membrane fusion and NPC assembly. When excess importin \u03b2 is added to a full Xenopus nuclear reconstitution reaction, vesicles are recruited to chromatin but their fusion is blocked. The importin \u03b2 down-regulation of membrane fusion is Ran-GTP reversible. Indeed, excess RanGTP (RanQ69L) alone stimulates excessive membrane fusion, leading to intranuclear membrane tubules and cytoplasmic annulate lamellae-like structures. We propose that a precise balance of importin \u03b2 to Ran is required to create a correct double nuclear membrane and simultaneously to repress undesirable fusion events. Interestingly, truncated importin \u03b2 45\u2013462 allows membrane fusion but produces nuclei lacking any NPCs. This reveals distinct importin \u03b2-regulation of NPC assembly. Excess full-length importin \u03b2 and \u03b2 45\u2013462 act similarly when added to prefused nuclear intermediates, i.e., both block NPC assembly. The importin \u03b2 NPC block, which maps downstream of GTP\u03b3S and BAPTA-sensitive steps in NPC assembly, is reversible by cytosol. Remarkably, it is not reversible by 25 \u03bcM RanGTP, a concentration that easily reverses fusion inhibition. This report, using a full reconstitution system and natural chromatin substrates, significantly expands the repertoire of importin \u03b2. Its roles now encompass negative regulation of two of the major events of nuclear assembly: membrane fusion and NPC assembly.<\/jats:p>","DOI":"10.1091\/mbc.e03-05-0275","type":"journal-article","created":{"date-parts":[[2003,8,12]],"date-time":"2003-08-12T02:37:42Z","timestamp":1060655862000},"page":"4387-4396","source":"Crossref","is-referenced-by-count":137,"title":["Importin \u03b2 Negatively Regulates Nuclear Membrane Fusion and Nuclear Pore Complex Assembly"],"prefix":"10.1091","volume":"14","author":[{"given":"Amnon","family":"Harel","sequence":"first","affiliation":[{"name":"Section of Cell and Developmental Biology, Division of Biological Sciences 0347, University of California, San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, Division of Biological Sciences 0347, University of California, San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Lachish-Zalait","sequence":"additional","affiliation":[{"name":"Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Elbaum","sequence":"additional","affiliation":[{"name":"Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglass J.","family":"Forbes","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, Division of Biological Sciences 0347, University of California, San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Allen, N.P., Patel, S.S., Huang, L., Chalkley, R.J., Burlingame, A., Lutzmann, M., Hurt, E.C., and Rexach, M. 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