Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes
Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes作者机构：Institute of Cellular and System Medicine'National' Health Research Institutes Miaoli 350 Department of Physiology and Biophysics 'National' Defense Medical Center Taipei 114 Institute of Biomedical Engineering 'National' Tsing Hua University Hsinchu 300 Institute of Biomedical Engineering 'National' Cheng Kung University Tainan 701
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2014年第8卷第6期
页 面：458-472页
核心收录：
学科分类：090603[农学-临床兽医学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 09[农学] 0906[农学-兽医学] 10[医学]
基 金：“Ministry”ofScienceandTechnologygrants(MOST-103-2321-B-400-001 MOST-103-2325-B-016-003)
主 题：deformability directionality migration PKCs T-lymphocyte
摘 要：T-tym phocyte migration under flow is critical for immune responses, but the mechanisms by which flow modulates the migratory beha- viors of T-lymphocytes remain unclear. Human peripheral blood T-lymphocytes （PBTLs）, when stimulated with phorboL 12-myristate 13-acetate （PMA）, stretched their ceU bodies dramatically and moved alongthe flow direction. In contrast, stromal ceil-derived factor- lα-stimulated PBTI.s 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-β1 in the microtubuie organizing center, and PKC-1311 in the uropod and peripheral region. PKC-δ regulated cell protrusions in the leading edge through Tiaml/Racl/caLmoduUn, 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 modu｜ate the directionality and deformability of migratory T-Lymphocytes under flow.
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