Progesterone Receptor Membrane Component-1 (PGRMC1) and PGRMC-2 Interact to Suppress Entry into the Cell Cycle in Spontaneously Immortalized Rat Granulosa Cells.

Progesterone Receptor Membrane Component-1 (PGRMC1) and PGRMC-2 Interact to Suppress Entry into the Cell Cycle in Spontaneously Immortalized Rat Granulosa Cells. Biol Reprod. 2014 Sep 24; Authors: Peluso JJ, Griffin D, Liu X, Horne M Abstract Progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 are expressed in rat granulosa cells and spontaneously immortalized granulosa cells (SIGCs) but their biological roles are not well defined. The present studies demonstrate that depleting either Pgrmc1 or Pgrmc2 in SIGCs increases entry into the cell cycle but does not increase cell proliferation. Rather PGRMC1 and/or PGRMC2-deplete cells accumulate in metaphase and undergo apoptosis. Since both PGRMC1 and PGRMC2 localize to the mitotic spindle, their absence likely accounts for cells arresting in metaphase. Moreover, pull-down assays, co-localization studies and in situ proximity ligation assays (PLA) indicate that PGRMC1 binds PGRMC2. Disrupting the PGRMC1: PGRMC2 complex through the use of siRNA or the cytoplasmic delivery of a PGRMC2 antibody increases entry into the cell cycle. Conversely, over expressing either PGRMC1-GFP or GFP-PGRMC2 fusion protein inhibits entry into the cell cycle. Subsequent studies reveal that depleting PGRMC1 and/or PGRMC2 reduces the percentage of cells in G0 and increases the percentage of cells in G1. These observations indicate that in addition to their role at metaphase PGRMC1 and PGRMC2 are involve...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research