title: PTEN regulates motility but not directionality during leukocyte chemotaxis.
abstract: The localization at opposite cell poles of phosphatidylinositol-3 kinases and PTEN (phosphatase and tensin homolog on chromosome 10) governs Dictyostelium chemotaxis. To study this model in mammalian cells, we analyzed the dynamic redistribution of green fluorescent protein (GFP)-tagged PTEN chimeras during chemotaxis. N- or C-terminus GFP-tagged PTEN was distributed homogeneously in the cytoplasm of chemotaxing PTEN-negative Jurkat cells and PTEN-positive HL60 cells. Moreover, we did not detect uropod accumulation of endogenous PTEN in chemoattractant-stimulated HL60 cells. Cell fractionation indicated that both endogenous and ectopically expressed PTEN were confined largely to the cytosol, and that chemoattractant stimulation did not alter this location. PTEN re-expression in Jurkat cells or PTEN depletion by specific siRNA in HL60 cells did not affect cell gradient sensing; PTEN nonetheless modulated chemoattractant-induced actin polymerization and the speed of cell movement. The results suggest a role for PTEN in regulating actin polymerization, but not directionality during mammalian cell chemotaxis.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Rosa Ana
authors.initials: RA
authors.lastname: Lacalle
authors.forename: Concepción
authors.initials: C
authors.lastname: Gómez-Moutón
authors.forename: Domingo F
authors.initials: DF
authors.lastname: Barber
authors.forename: Sonia
authors.initials: S
authors.lastname: Jiménez-Baranda
authors.forename: Emilia
authors.initials: E
authors.lastname: Mira
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carrera
authors.forename: Santos
authors.initials: S
authors.lastname: Mañes
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002384:Catalysis; D002465:Cell Movement; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology*; D021962:Membrane Microdomains / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D002630:Chemotactic Factors; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human