Identification and characterization of an alternatively spliced variant of the MHC class I-related porcine neonatal Fc receptor for IgG.
The neonatal Fc receptor for immunoglobulin G (IgG) (FcRn) functions to transport maternal IgG to the fetal/neonatal animals and protects IgG from catabolism. The present study identified two pFcRn cDNAs (1.071 and 0.795kb) from intestinal epithelial cells. The corresponding mRNA transcripts were detected in porcine kidney cell line LLC-PK1, peripheral blood mononuclear cells, and porcine tissues by reverse transcription-PCR (RT-PCR) and Northern blot. Sequence analysis showed that the 1.071kb cDNA encodes the full-length pFcRn (pFcRn-L), whereas the 0.795kb cDNA codes for a truncated pFcRn (pFcRn-S) with deletion of 92 amino acids matching the alpha2 domain of pFcRn-L. pFcRn-L was constitutively expressed by epithelial cells; however, pFcRn-S was not detectable in porcine tissues and cell lines although its transcript was abundant. Despite the lack of native pFcRn-S, pFcRn-S was readily detected in transfected cells. Recombinant pFcRn-L was confirmed to bind IgG at pH 6.0, but not at pH 7.5; however, pFcRn-S failed to bind IgG at both pH 5.0-6.0 and 7.5. pFcRn-L was expressed on the cell surface and mainly localized in early endosomes. In contrast, pFcRn-S was absent from cell surface and primarily localized in the lysosome and pFcRn-S trafficking to lysosomes was independent of beta(2)-microglobulin (beta(2)m). The accumulation of pFcRn-S in the lysosome may explain the absence of native pFcRn-S protein expression. In addition, the trafficking of pFcRn-S to the lysosomal compartment suggests that in addition to sorting signals in its cytoplasmic tail, the FcRn structural integrity may be important for proper intracellular trafficking and function.
Ye
Lilin
L
Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
Tuo
Wenbin
W
Liu
Xindong
X
Simister
Neil E
NE
Zhu
Xiaoping
X
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017452:Receptors, IgG / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D013552:Swine / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000502:physiology
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D017452:Receptors, IgG; D001613:beta 2-Microglobulin