Microtubule asymmetry during neutrophil polarization and migration.
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.
Eddy
Robert J
RJ
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
Pierini
Lynda M
LM
Maxfield
Frederick R
FR
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
D001381:Azepines; D005353:Fibronectins; D018960:Hyaluronan Receptors; D009281:Naphthalenes; C070571:ML 7; D015638:Cytochalasin D