Neutrophil microtubules suppress polarity and enhance directional migration

Jingsong Xu, Fei Wang, Alexandra Van Keymeulen, Maike Rentel, Henry R. Bourne

Research output: Contribution to journalArticle

Abstract

How do microtubules, which maintain and direct polarity of many eukaryotic cells, regulate polarity of blood neutrophils? In sharp contrast to most cells, disrupting a neutrophil's microtubule network with nocodazole causes it to polarize and migrate [Niggli, V. (2003) J. Cell Sci. 116, 813-822]. 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 "backness" and "frontness" signals responsible for neutrophil polarity. Nocodazole (i) stimulates backness by increasing Rho- and actomyosin-dependent contractility, as reported by Niggli, and also (ii) 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′-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.

Original languageEnglish (US)
Pages (from-to)6884-6889
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number19
DOIs
StatePublished - May 10 2005

Keywords

  • Chemotaxis
  • PIP3
  • Pseudopod
  • Rho GTPases

ASJC Scopus subject areas

  • General

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