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Exclusion of exogenous phosphatidylinositol‐3,4,5‐trisphosphate from neutrophil‐polarizing pseudopodia: stabilization of the uropod and cell polarity
Author(s) -
Tian Wei,
Laffafian Iraj,
Dewitt Sharon,
Hallett Maurice B
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor947
Subject(s) - pseudopodia , phosphatidylinositol , microbiology and biotechnology , chemotaxis , cell polarity , biology , biophysics , phosphorylation , actin , cell , biochemistry , receptor
Although there is accumulating evidence that the generation and localization of phosphatidylinositol‐3,4,5‐trisphosphate (PtdIns(3,4,5)P 3 ) have important functions in neutrophil polarization and chemotaxis, the mechanism of this linkage has yet to be established. Here, using exogenous fluorescent PtdIns(3,4,5)P 3 introduced into the inner leaflet of the neutrophil plasma membrane by a cationic carrier, we show that: first, PtdIns(3,4,5)P 3 uniformly delivered to the neutrophil plasma membrane is excluded from newly forming pseudopodia; second, PtdIns(3,4,5)P 3 translocates to and is immobilized at the pole opposite a stable polarizing pseudopod; third, asymmetric delivery of PtdIns(3,4,5)P 3 to the neutrophil triggers the generation of polarizing pseudopodia at the opposite pole; and finally, PtdIns(3,4,5)P 3 triggers repetitive Ca 2+ signals, the onset of which precedes morphological polarization. These data suggest that translocation and immobilization of PtdIns(3,4,5)P 3 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.