Roles of extracellular and intracellular sphingosine 1-phosphate in cell migration.
Sphingosine 1-phosphate (S1P) is an important factor for the regulation of cell motility acting both inside and outside the cells. The precise role of S1P in the control of cell motility, however, remains unclear. Here we describe the roles of S1P in the regulation of cell motility by dissecting them into intracellular and extracellular actions using a liposomal S1P transfer technique. In a Boyden chamber assay free S1P enhanced directional cell movement, whereas liposomal S1P induced nondirectional cell movement. Furthermore, inhibition of sphingosine kinase (SphK) 1 by several inhibitors or knockdown of the enzyme expression by siRNA caused reduced wound-faced cell polarity formation as assessed by wound-healing assay. Moreover, S1P-induced cell migration was strongly inhibited by SphK inhibitors. These results indicate that extracellular S1P acting through S1P receptors facilitates the formation of cell polarity, whereas S1P generated inside the cells functions as an intracellular mediator per se to enhance nondirectional cell movement, thus S1P enhances directional cell movement in a coordinated fashion.
Yu
Huan
H
Division of Biochemistry, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Okada
Taro
T
Kobayashi
Masako
M
Abo-Elmatty
Dina M
DM
Jahangeer
Saleem
S
Nakamura
Shun-Ichi
S
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000099157:Sphingosine Kinase
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate