Fcgamma receptor transmembrane domains: role in cell surface expression, gamma 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 gamma chain-dependent Fcgamma receptors FcgammaRIIIA and FcgammaRI. FcgammaR chimeras containing the TM and cytoplasmic (CY) domains of the gamma chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcgammaRIIIA TM were poorly expressed. Receptors containing the FcgammaRI TM and the gamma chain CY but lacking the gamma chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a gamma chain dimer induced by the gamma chain TM is not required for efficient phagocytosis. Cotransfection of FcgammaRI or FcgammaRIIIA with the chimera CD8-gamma-gamma (EC-TM-CY) resulted in FcgammaR cell surface expression and phagocytosis, whereas CD8-CD8-gamma, whose TM does not associate with FcgammaR, allowed cell surface expression of (but not phagocytosis by) FcgammaRI. CD8-CD8-gamma also did not allow surface expression of FcgammaRIIIA. Exchanging FcgammaRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcgammaRI TM are essential for association of FcgammaRI with the gamma chain and phagocytosis. The data indicate that specific sequences in the FcgammaRIIIA and FcgammaRI TMs govern their different interactions with the gamma chain in cell surface expression and phagocytosis and that gamma chain TM sequences are not required for gamma chain-mediated phagocytosis. The data identify a specific region of the FcgammaRI TM and its asparagine as important for FcgammaRI cell surface expression in the absence of the gamma chain and for distinguishing the FcgammaRI and FcgammaRIIIA phenotypes.
Kim
Moo-Kyung
MK
Department of Medicine,University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Huang
Zhen-Yu
ZY
Hwang
Pyoung-Han
PH
Jones
Brian A
BA
Sato
Norihito
N
Hunter
Sharon
S
Kim-Han
Tai-Hee
TH
Worth
Randall G
RG
Indik
Zena K
ZK
Schreiber
Alan D
AD
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D004912:Erythrocytes; D009154:Mutation; D010587:Phagocytosis; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012756:Sheep; D014162:Transfection
D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins