Dual Functions of SLCO2A1 as Maxi-Cl Channel and PG Transporter

Solute carrier organic anion transporter family member 2A1 (SLCO2A1) is known to be a molecule responsible for prostaglandin transporter (PGT). Recently, SLCO2A1 was, in addition, identified as the core (pore-forming) molecule of large-conductance maxi-anion channel (Maxi-Cl) that is activated by cell swelling, is sensitive to Gd3+, and has a large pore size mediating ATP release. Thus, this protein exhibits transporter/channel dual functions. In the same cell types, SLCO2A1 molecules were found to simultaneously exhibit both PGT and Maxi-Cl activities in a manner independent of each other. Thus, it is suggested that there exist two groups of SLCO2A1 molecules, in parallel, the activation mechanisms of which are differently regulated. After making genome-wide survey for the molecules involved in the activation mechanism of Maxi-Cl/SLCO2A1, the ANXA2-S100A10 complex was identified as its regulatory subunit by conferring protein tyrosine dephosphorylation and cytosolic Ca2+ dependence thereon. In contrast, SLCO2A1 was shown to exhibit PGT activity by physically interacting with ANXA2 alone. In addition, decreased expression of S100A10 was found to augment plasmalemmal SLCO2A1 expression, thereby augmenting PGT/SLCO2A1 activity. In conclusion, current evidence indicates that SLCO2A1 can exert dual functions as ANXA2-S100A10-associated Maxi-Cl activity and S100A10-lacking ANXA2-associated PGT activity in a manner dependent on the S100A10 expression level. From this standpoint, future studies are warranted to be performed on the three-dimensional conformation changes between PGT and Maxi-Cl and physiological/pathological relevance of SLCO2A1.

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