title: Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes.
abstract: T-lymphocyte migration under flow is critical for immune responses, but the mechanisms by which flow modulates the migratory behaviors of T-lymphocytes remain unclear. Human peripheral blood T-lymphocytes (PBTLs), when stimulated with phorbol 12-myristate 13-acetate (PMA), stretched their cell bodies dramatically and moved along the flow direction. In contrast, stromal cell-derived factor-1α-stimulated PBTLs deformed and migrated in a random manner. Here we elucidated the molecular mechanisms underlying flow-induced directionality and deformation of PMA-stimulated PBTLs. PMA primed PBTLs for polarization under flow, with protein kinase C (PKC)-δ enriched in the leading edge, PKC-βI in the microtubule organizing center, and PKC-βII in the uropod and peripheral region. PKC-δ regulated cell protrusions in the leading edge through Tiam1/Rac1/calmodulin, whereas PKC-β regulated RhoA/Rho-associated kinase activity and microtubule stability to modulate uropod contractility and detachment. Our findings indicate that PKC-δ and -β coordinate in the cell leading edge and uropod, respectively, to modulate the directionality and deformability of migratory T-lymphocytes under flow.
authors.affiliation: Institute of Cellular and System Medicine, 'National' Health Research Institutes, Miaoli 350.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Wei
authors.affiliation: Institute of Cellular and System Medicine, 'National' Health Research Institutes, Miaoli 350.
authors.forename: Ting-Er
authors.initials: TE
authors.lastname: Lin
authors.affiliation: Institute of Cellular and System Medicine, 'National' Health Research Institutes, Miaoli 350.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Institute of Cellular and System Medicine, 'National' Health Research Institutes, Miaoli 350.
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biophysics, 'National' Defense Medical Center, Taipei 114.
authors.forename: Min-Chien
authors.initials: MC
authors.lastname: Tsai
authors.affiliation: Institute of Cellular and System Medicine, 'National' Health Research Institutes, Miaoli 350 Institute of Biomedical Engineering, 'National' Tsing Hua University, Hsinchu 300 Institute of Biomedical Engineering, 'National' Cheng Kung University, Tainan 701 jjchiu@nhri.org.tw.
authors.forename: Jeng-Jiann
authors.initials: JJ
authors.lastname: Chiu
mesh_terms: D002273:Carcinogens / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000201:enzymology; D006801:Humans; D064546:Protein Kinase C beta / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D002273:Carcinogens; D020662:Guanine Nucleotide Exchange Factors; C107953:RAC1 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C066737:RHOA protein, human; C579054:PRKCB protein, human; C497258:PRKCD protein, human; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D013755:Tetradecanoylphorbol Acetate
keywords: PKCs; T-lymphocyte; deformability; directionality; migration