Fc receptor transmembrane domains: role in cell surface expression, chain interaction, and phagocytosis

We constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the chain–dependent Fc receptors Fc RIIIA and Fc RI. Fc R chimeras containing the TM and cytoplasmic (CY) domains of the chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the Fc RIIIA TM were poorly expressed. Receptors containing the Fc RI TM and the chain CY but lacking the chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a chain dimer induced by the chain TM is not required for efficient phagocytosis. Cotransfection of Fc RI or Fc RIIIA with the chimera CD8(EC-TM-CY) resulted in Fc R cell surface expression and phagocytosis, whereas CD8-CD8, whose TM does not associate with Fc R, allowed cell surface expression of (but not phagocytosis by) Fc RI. CD8-CD8also did not allow surface expression of Fc RIIIA. Exchanging Fc RI and CD8 TMs indicated that the C-terminal 11 amino acids of the Fc RI TM are essential for association of Fc RI with the chain and phagocytosis. The data indicate that specific sequences in the Fc RIIIA and Fc RI TMs govern their different interactions with the chain in cell surface expression and phagocytosis and that chain TM sequences are not required for chain– mediated phagocytosis. The data identify a specific region of the Fc RI TM and its asparagine as important for Fc RI cell surface expression in the absence of the chain and for distinguishing the Fc RI and Fc RIIIA phenotypes. (Blood. 2003; 101:4479-4484)