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

Journal of Cell Science
Hiroshi YukiuraJunken Aoki

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 in mice causes similar vascular defects, indicating that the extracellular amount of LPA must 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 was missing 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 ...Continue Reading

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Citations

Sep 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew J Morris, Susan S Smyth
Sep 22, 2018·Protein Science : a Publication of the Protein Society·Martin Audet, Raymond C Stevens
Dec 22, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Davide GnocchiAntonio Mazzocca
Jul 25, 2019·The Journal of Clinical Investigation·Daisuke YasudaSatoshi Ishii
Dec 18, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric EngelbrechtTimothy Hla
Aug 2, 2019·Biochemistry and Biophysics Reports·Yuki ShibaikeKimiko Murakami-Murofushi
Jul 14, 2018·Molecular Therapy. Methods & Clinical Development·Silvia AldiEva Hurt-Camejo

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