A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression

Abstract

Treatment of different cell lines with progesterone receptor membrane component 1 (PGRMC1) antagonist AG-205 rapidly induces the formation of large vesicular structures that likely represent endosomes. Crispr/Cas9 was used to target the PGRMC1 and progesterone receptor membrane component 2 (PGRMC2) genes in CHO-K1 and HeLa. Unexpectedly, deficiency in one of these or both genes did not inhibit the formation of enlarged vesicles by AG-205, demonstrating additional molecular target(s) of this compound besides PGRMC1. Thus, AG-205 cannot be regarded as a PGRMC1-specific antagonist. However, provided that its currently unknown target(s) will be identified, AG-205 may serve as a new reagent to study endosomal trafficking.