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PMID:23667561

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Citation

Usatyuk, PV, Burns, M, Mohan, V, Pendyala, S, He, D, Ebenezer, DL, Harijith, A, Fu, P, Huang, LS, Bear, JE, Garcia, JG and Natarajan, V (2013) Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction. PLoS ONE 8:e63007

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.

Links

PubMed PMC3648575 Online version:10.1371/journal.pone.0063007

Keywords

Blotting, Western; Cells, Cultured; Chemotaxis/drug effects; Chemotaxis/physiology; Endothelial Cells/drug effects; Endothelial Cells/physiology; Gene Expression Regulation/drug effects; Humans; Lysophospholipids/pharmacology; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Microscopy, Fluorescence; Phospholipase D/metabolism; Protein Kinase C/metabolism; Protein Transport/drug effects; Pulmonary Artery/cytology; RNA Interference; RNA, Small Interfering/genetics; Signal Transduction/physiology; Sphingosine/analogs & derivatives; Sphingosine/pharmacology; rac1 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:COR1B

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

located_in

GO:0030027: lamellipodium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

involved_in

GO:0042060: wound healing

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

involved_in

GO:0035767: endothelial cell chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

involved_in

GO:0035767: endothelial cell chemotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:COR1B

GO:0035767: endothelial cell chemotaxis

ECO:0000315:

P

Fig 5

complete
CACAO 9416

HUMAN:COR1B

Contributes to

GO:0035767: endothelial cell chemotaxis

ECO:0000314:

P

Rac1 plays a role in S1P-induced redistribution of coronin 1B and cortactin to cell periphery as well as chemotaxis of human pulmonary artery endothelial cells. (Figure 7)

complete
CACAO 9417

HUMAN:COR1B

involved_in

GO:0042060: wound healing

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

involved_in

GO:0035767: endothelial cell chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

part_of

GO:0030027: lamellipodium

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000115)

Seeded From UniProt

complete

HUMAN:COR1B

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000115)

Seeded From UniProt

complete

See also

References

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