title: Microtubule asymmetry during neutrophil polarization and migration.
abstract: The development of cell polarity in response to chemoattractant stimulation in human polymorphonuclear neutrophils (PMNs) is characterized by the rapid conversion from round to polarized morphology with a leading lamellipod at the front and a uropod at the rear. During PMN polarization, the microtubule (MT) array undergoes a dramatic reorientation toward the uropod that is maintained during motility and does not require large-scale MT disassembly or cell adhesion to the substratum. MTs are excluded from the leading lamella during polarization and motility, but treatment with a myosin light chain kinase inhibitor (ML-7) or the actin-disrupting drug cytochalasin D causes an expansion of the MT array and penetration of MTs into the lamellipod. Depolymerization of the MT array before stimulation caused 10% of the cells to lose their polarity by extending two opposing lateral lamellipodia. These multipolar cells showed altered localization of a leading lamella-specific marker, talin, and a uropod-specific marker, CD44. In summary, these results indicate that F-actin- and myosin II-dependent forces lead to the development and maintenance of MT asymmetry that may act to reinforce cell polarity during PMN migration.
authors.affiliation: Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Eddy
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Pierini
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Maxfield
mesh_terms: D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: D001381:Azepines; D005353:Fibronectins; D018960:Hyaluronan Receptors; D009281:Naphthalenes; C070571:ML 7; D015638:Cytochalasin D