LPP3 localizes LPA6 signalling to non-contact sites in endothelial cells

Hiroshi Yukiura, Kuniyuki Kano, Ryoji Kise, Asuka Inoue, Junken Aoki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) is emerging as an angiogenic factor, because knockdown of the enzyme that produces it (autotaxin, also known as ENPP2) and its receptors cause severe developmental vascular defects in both mice and fish. In addition, overexpression of autotaxin inmice causes similar vascular defects, indicating that the extracellularamount of LPAmust be tightly regulated.Here,we focused on an LPA-degrading enzyme, lipid phosphate phosphatase 3 (LPP3, also known as PPAP2B), and showed that LPP3 was localized in specific cell-cell contact sites of endothelial cells and suppresses LPA signalling through the LPA6 receptor (also known as LPAR6). In HEK293 cells, overexpression of LPP3 dramatically suppressed activation of LPA6. In human umbilical vein endothelial cells (HUVECs), LPA induced actin stress fibre formation through LPA6, which was substantially upregulated by LPP3 knockdown. LPP3 was localized to cell-cell contact sites and wasmissing in non-contact sites to which LPA-induced actin stress fibre formation mediated by LPA6 was restricted. Interestingly, the expression of LPP3 in HUVECs was dramatically increased after forskolin treatment in a process involving Notch signalling. These results indicate that LPP3 regulates and localizes LPA signalling in endothelial cells, thereby stabilizing vessels through Notch signalling for proper vasculature.

Original languageEnglish
Pages (from-to)3871-3877
Number of pages7
JournalJournal of cell science
Volume128
Issue number21
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • Endothelial cell
  • LPA receptor
  • LPP3
  • Lysophosphatidic acid

ASJC Scopus subject areas

  • Cell Biology

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