Endogenous Jmjd6 Gene Product Is Expressed at the Cell Surface and Regulates Phagocytosis in Immature Monocyte-Like Activated THP-1 Cells

A jumonji domain containing gene 6 (Jmjd6), previously referred to as phosphatidylserine receptor (PSR) gene, plays an important role in cell differentiation and development of multiple organs, although mechanisms of its action are not known. The Jmjd6 gene product was initially identified as a membrane protein that participates in phagocytosis. However, the later findings that recombinant Jmjd6 in expression systems was targeted to the nucleus challenged the role of Jmjd6 as a membrane receptor. Using immunocytochemistry approach we studied the subcellular distribution of endogenous Jmjd6 protein in THIP-I cells activated with phorbol 12-myristate 13 acetate (IPMA). We found that treatment with PMA stimulated Jmjd6 expression in the cytosol of activated cells. Furthermore, Jmjd6 initially appeared at the cell surface of immature phagocytes (1-2 days after activation) but then translocated into the nucleus of differentiated macrophage-like cells (5-9 days after activation). Anti-Jmjd6 antibodies suppressed the engulfment of dead cell corpses by THP-I cells expressing the Jmjd6 at the cell surface. These data indicate that Jmjd6 serves as a membrane-associated receptor that regulates phagocytosis in immature macrophages but is dispensable for phagocytosis and has other functions when it is expressed in the cytosol and nucleus of mature macrophage-like cells. J. Cell. Physiol. 221: 84-91, 2009. (C) 2009 Wiley-Liss, Inc.