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Nocodazole induces the same responses in differentiated HL-60 cells, a model neutrophil cell line, and reduces their chemotactic prowess by causing them to pursue abnormally circuitous paths in migrating toward a stationary point source of an attractant, f-Met-Leu-Phe (fMLP). The chemotactic defect stems from dramatic nocodazole-induced imbalance between the divergent, opposed fMLP-induced \u201cbackness\u201d and \u201cfrontness\u201d signals responsible for neutrophil polarity. Nocodazole (<jats:italic>i<\/jats:italic>) stimulates backness by increasing Rho- and actomyosin-dependent contractility, as reported by Niggli, and also (<jats:italic>ii<\/jats:italic>) impairs fMLP-dependent frontness: pseudopods are flatter, contain less F-actin, and show decreased membrane translocation of PH-Akt-GFP, a fluorescent marker for 3\u2032-phosphoinositide lipids. Inhibiting backness with a pharmacologic inhibitor of a Rho-dependent kinase substantially reverses nocodazole's effects on chemotaxis, straightness of migration paths, morphology, and PH-Akt-GFP translocation. Thus, microtubules normally balance backness vs. frontness signals, preventing backness from reducing the strength of pseudopods and from impairing directional migration.<\/jats:p>","DOI":"10.1073\/pnas.0502106102","type":"journal-article","created":{"date-parts":[[2005,4,29]],"date-time":"2005-04-29T00:25:44Z","timestamp":1114734344000},"page":"6884-6889","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Neutrophil microtubules suppress polarity and enhance directional migration"],"prefix":"10.1073","volume":"102","author":[{"given":"Jingsong","family":"Xu","sequence":"first","affiliation":[{"name":"Departments of Cellular and Molecular Pharmacology and Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0450"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cellular and Molecular Pharmacology and Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0450"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Van Keymeulen","sequence":"additional","affiliation":[{"name":"Departments of Cellular and Molecular Pharmacology and Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0450"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maike","family":"Rentel","sequence":"additional","affiliation":[{"name":"Departments of Cellular and Molecular Pharmacology and Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0450"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry R.","family":"Bourne","sequence":"additional","affiliation":[{"name":"Departments of Cellular and Molecular Pharmacology and Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0450"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2005,4,28]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0703-599"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.21.3795"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000635200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00471-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01423"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408047"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200202032"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.89.3.585"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.75.2.606"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"Weiner O. 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