title: Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.
abstract: Coronins are a highly conserved family of actin binding proteins that regulate actin-dependent processes such as cell motility and endocytosis. We found that treatment of human pulmonary artery endothelial cells (HPAECs) with the bioactive lipid, sphingosine-1-phosphate (S1P) rapidly stimulates coronin 1B translocation to lamellipodia at the cell leading edge, which is required for S1P-induced chemotaxis. Further, S1P-induced chemotaxis of HPAECs was attenuated by pretreatment with small interfering RNA (siRNA) targeting coronin 1B (∼36%), PLD2 (∼45%) or Rac1 (∼50%) compared to scrambled siRNA controls. Down regulation PLD2 expression by siRNA also attenuated S1P-induced coronin 1B translocation to the leading edge of the cell periphery while PLD1 silencing had no effect. Also, S1P-induced coronin 1B redistribution to cell periphery and chemotaxis was attenuated by inhibition of Rac1 and over-expression of dominant negative PKC δ, ε and ζ isoforms in HPAECs. These results demonstrate that S1P activation of PLD2, PKC and Rac1 is part of the signaling cascade that regulates coronin 1B translocation to the cell periphery and the ensuing cell chemotaxis.
authors.affiliation: Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Usatyuk
authors.forename: Michael
authors.initials: M
authors.lastname: Burns
authors.forename: Vijay
authors.initials: V
authors.lastname: Mohan
authors.forename: Srikanth
authors.initials: S
authors.lastname: Pendyala
authors.forename: Donghong
authors.initials: D
authors.lastname: He
authors.forename: David L
authors.initials: DL
authors.lastname: Ebenezer
authors.forename: Anantha
authors.initials: A
authors.lastname: Harijith
authors.forename: Panfeng
authors.initials: P
authors.lastname: Fu
authors.forename: Long Shuang
authors.initials: LS
authors.lastname: Huang
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010739:Phospholipase D / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D008840:Microfilament Proteins; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; C072061:coronin proteins; C060506:sphingosine 1-phosphate; D011493:Protein Kinase C; C105606:phospholipase D2; D010739:Phospholipase D; D020830:rac1 GTP-Binding Protein; D013110:Sphingosine