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Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes Free
Shu-Yi Wei1, Ting-Er Lin1, Wei-Li Wang1, Pei-Ling Lee1, Min-Chien Tsai2, and Jeng-Jiann Chiu1,3,4,*
1Institute of Cellular and System Medicine, ‘National’ Health Research Institutes, Miaoli 350
2Department of Physiology and Biophysics, ‘National’ Defense Medical Center, Taipei 114
3Institute of Biomedical Engineering, ‘National’ Tsing Hua University, Hsinchu 300
4Institute of Biomedical Engineering, ‘National’ Cheng Kung University, Tainan 701 *Correspondence to:Jeng-Jiann Chiu, E-mail: jjchiu@nhri.org.tw
J Mol Cell Biol, Volume 6, Issue 6, December 2014, Pages 458-472  https://doi.org/10.1093/jmcb/mju050
Keyword: deformability, directionality, migration, PKCs, T-lymphocyte

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.