Identification of Four Mouse FcRn Splice Variants and FcRn-Specific Vesicles

Authors:

George Haddad, Judith Blaine

Keywords:

neonatal Fc receptor; alternatively spliced variants; vesicular transport; immunoglobulin; albumin; immune complexes; cellular recycling; podocytes

Abstract:

Research into the neonatal Fc receptor (FcRn) has increased dramatically ever since Simister and Mostov first purified a rat version of the receptor. Over the years, FcRn has been shown to function not only as a receptor that transfers immunity from mother to fetus but also performs an array of different functions that include transport and recycling of immunoglobulins and albumin in the adult. Due to its important cellular roles, several clinical trials have been designed to either inhibit/enhance FcRn function or develop of non-invasive therapeutic delivery system such as fusion of drugs to IgG Fc or albumin to enhance delivery inside the cells. Here, we report the accidental identification of several FcRn alternatively spliced variants in both mouse and human cells. The four new mouse splice variants are capable of binding immunoglobulins’ Fc and Fab portions. In addition, we have identified FcRn-specific vesicles in which immunoglobulins and albumin can be stored and that are involved in the endosomal–lysosomal system. The complexity of FcRn functions offers significant potential to design and develop novel and targeted therapeutics.

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