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Title: Identification and characterization of a novel splicing variant of the MHC class 1-related neonatal Fe receptor for IgG.

Author
item YE, LILIN - U MD COLLEGE PARK MD
item Tuo, Wenbin
item LIU, XINDONG - U MD COLLEGE PARK MD
item ZHU, XIAOPING - U MD COLLEGE PARK MD

Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2007
Publication Date: 2/20/2008
Citation: Ye, L., Tuo, W., Liu, X., Zhu, X. 2008. Identification and characterization of an alternatively spliced variant of the MHC class I-related porcine neonatal Fc receptor for IgC. Dev Comp Immunol. 32(8):966-79. PMID:18321573

Interpretive Summary: VThe neonatal Fc receptor for IgG (FcRn), a MHC class I-related molecule, functions to transport maternal IgG to the fetus or newborn via placenta or intestine and protects IgG from catabolism. In the course of cloning porcine FcRn from the intestinal epithelial cell line IPEC, two cDNAs were identified: a long form of 1.071 kb (pFcRn-L) and a short variant of 0.795 kb (pFcRn-S). The corresponding mRNA transcripts were detected in porcine kidney epithelial cell line LLC-PK1, peripheral blood mononuclear cells, as well as a variety of porcine tissues by RT-PCR and Northern blot. Sequence analysis showed that pFcRn-L cDNA encodes the full-length pFcRn, whereas pFcRn-S cDNA represents a splicing variant of pFcRn, coding for a truncated pFcRn with deletion of 92 amino acids matching to the alpha2 domain of pFcRn-L. Recombinant pFcRn-L bound IgG at pH 6.0, but not at pH 7.5. However, recombinant pFcRn-S bound IgG at both pH 5.0-6.0 and pH 7.5. Furthermore, the intracellular trafficking patterns of pFcRn-L and pFcRn-S exhibited remarkable differences. The pFcRn-L was expressed on the cell surface and mainly localized in early endosomal compartment, whereas pFcRn-S was absent from cell surface and primarily found in late endosome/lysosome. In contrast to pFcRn-L, pFcRn-S was destined to enter the lysosomal compartment and its trafficking to the lysosome was independent of '2m expression as shown using the '2m-deficient FO-1 cell line. These results suggest that pFcRn-S, independent of pH for IgG binding and of '2m for intracellular trafficking, may function differently in lysosomal compartment. Therefore, the results of these studies demonstrate that the complexity of FcRn function and regulation is diversified by RNA splicing, further implying the functional multiplicity of the FcRn receptors.

Technical Abstract: The neonatal Fc receptor for IgG (FcRn), a MHC class I-related molecule, functions to transport maternal IgG to the fetus or newborn via placenta or intestine and protects IgG from catabolism. In the course of cloning porcine FcRn from the intestinal epithelial cell line IPEC, two cDNAs were identified: a long form of 1.071 kb (pFcRn-L) and a short variant of 0.795 kb (pFcRn-S). The corresponding mRNA transcripts were detected in porcine kidney epithelial cell line LLC-PK1, peripheral blood mononuclear cells, as well as a variety of porcine tissues by RT-PCR and Northern blot. Sequence analysis showed that pFcRn-L cDNA encodes the full-length pFcRn, whereas pFcRn-S cDNA represents a splicing variant of pFcRn, coding for a truncated pFcRn with deletion of 92 amino acids matching to the alpha2 domain of pFcRn-L. Recombinant pFcRn-L bound IgG at pH 6.0, but not at pH 7.5. However, recombinant pFcRn-S bound IgG at both pH 5.0-6.0 and pH 7.5. Furthermore, the intracellular trafficking patterns of pFcRn-L and pFcRn-S exhibited remarkable differences. The pFcRn-L was expressed on the cell surface and mainly localized in early endosomal compartment, whereas pFcRn-S was absent from cell surface and primarily found in late endosome/lysosome. In contrast to pFcRn-L, pFcRn-S was destined to enter the lysosomal compartment and its trafficking to the lysosome was independent of '2m expression as shown using the '2m-deficient FO-1 cell line. These results suggest that pFcRn-S, independent of pH for IgG binding and of '2m for intracellular trafficking, may function differently in lysosomal compartment. Therefore, the results of these studies demonstrate that the complexity of FcRn function and regulation is diversified by RNA splicing, further implying the functional multiplicity of the FcRn receptors.