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- Title
Exclusion of exogenous phosphatidylinositol-3,4,5-trisphosphate from neutrophil-polarizing pseudopodia: stabilization of the uropod and cell polarity.
- Authors
Tian, Wei; Laffafian, Iraj; Dewitt, Sharon; Hallett, Maurice B.
- Abstract
Although there is accumulating evidence that the generation and localization of phosphatidylinositol-3,4,5-triphosphate (Ptdlns(3,4,5)P3 have important functions in neutrophil polarization and chemotaxis the mechanism of this linkage has yet to be established. Here, using exogenous fluorescent Ptdlns(3,4,5)P3 introduced into the inner leaflet of the neutrophil plasma membrane by a cationic carrier, we show that first, Ptdlns (3,4,5)P3 uniformly delivered to the neutrophil plasma membrane is excluded from newly forming pseudopodia; second, Ptdlns(3,4,5) P3 transiocates to and is immobilized at the pole opposite a stable polarizing pseudopod; third, asymmetric delivery of Ptdlns(3,4,5)P3 to the neutrophil triggers the generation of polarizing pseudopodia at the opposite pole; and finally, Ptdlns(3,4,5)P3 triggers repetitive Ca2+ signals, the onset of which precedes morphological polarization. These data suggest that translocation and immo- bilization of Ptdlns(3,4,5)P3 or a 3,x-phosphorylated metabolite in the uropod functions as an important polarization cue that defines neutrophil polarity and stabilizes the generation of pseudopodia at the opposite pole.
- Subjects
PHOSPHOINOSITIDES; NEUTROPHILS; UROPODA; CELL populations; CELL membranes; PHOSPHATES
- Publication
EMBO Reports, 2003, Vol 4, Issue 10, p982
- ISSN
1469-221X
- Publication type
Article
- DOI
10.1038/sj.embor.embor947