Modulation of prostaglandin transport activity of SLCO2A1 by annexin A2 and S100A10

This study examined PGE2 uptake and ATP release in Anxa2 and/or S100a10 knockout (KO) murine breast C127 cells. Deletion of Slco2a1 decreased PGE2-d4 uptake by wild-type (WT) cells in isotonic medium (290 mOsm/kg H2O). Decreased osmolarity (135 mOsm/kg H2O) stimulated ATP release but didn't affect PGE2 uptake kinetics, showing Km (1280 nM) and Vmax (10.38 pmol/15 sec/mg protein) similar to those in isotonic medium (1227 nM and 10.65 pmol/15 sec/mg protein), respectively, in WT cells. Deletion of Anxa2 associated with loss of S100a10 diminished SLCO2A1-mediated ATP release and uncompetitively inhibited PGE2 uptake with lowered Km (376 nM) and Vmax(2.59 pmol/15 sec/mg protein). Moreover, the immunoprecipitation assay confirmed the physical interaction of ANXA2 with SLCO2A1 in WT cells. Enforcement of ANXA2 expression to Anxa2 KO cells partially restored PGE2 uptake and increased Km (744.3 nM) and Vmax(9.07 pmol/15 sec/mg protein); while the uptake clearance (Vmax/Km) didn't change much regardless of ANXA2 expression. These results suggest that an ANXA2/S100A10 complex modulates PG transport activity but osmolality has little effect on it; therefore, the bound form of SLCO2A1, which functions as a PG transporter and Maxi-Cl, may exist regardless of changes in the cell volume.PMID:38372137 | DOI:10.1152/ajpcell.00701.2023

Source: Am J Physiol Cell Ph... - February 19, 2024 Category: Cytology Authors: Yoshinobu Nakamura Masa-Aki Ito Yukino Hoshino Isao Matsuoka Toshiaki Okada Yasunobu Okada Takeo Nakanishi Source Type: research