Abstract
Epithelial cells have separate apical and basolateral plasma membrane domains with distinct compositions. After delivery to one surface, proteins can be endocytosed and then recycled, degraded or transcytosed to the opposite surface. Proper sorting into the transcytotic pathway is essential for maintaining polarity, as most proteins are endocytosed many times during their lifespan1. The polymeric immunoglobulin receptor (pIgR) transcytoses polymeric IgA (pIgA) from the basolateral to the apical surface of epithelial cells and hepatocytes2,3. However, the molecular machinery that controls polarized sorting of pIgR–pIgA and other receptors is only partially understood. The retromer is a multimeric protein complex, originally described in yeast, which mediates intracellular sorting of Vps10p, a receptor that transports vacuolar enzymes4. The yeast retromer contains two sub-complexes. One includes the Vps5p and Vps17p subunits, which provide mechanical force for vesicle budding5,6. The other is the Vps35p–Vps29p–Vps26p subcomplex, which provides cargo specificity7. The mammalian retromer binds to the mannose 6-phosphate receptor, which sorts lysosomal enzymes from the trans-Golgi network to the lysosomal pathway8,9. Here, we show a function for the mammalian Vps35–Vps29–Vps26 retromer subcomplex in promoting pIgR–pIgA transcytosis.
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Acknowledgements
We thank J.S. Bonifacino and M.N.J. Seaman for copies of their papers before publication and we thank the following UCSF facilities for providing us infrastructure and/or services to perform our studies: the Molecular Structure Core of the Liver Center (P30 DK 26743), the Biomolecular Resource Center, and the Laboratory for Cell Analysis of the Comprehensive Cancer Center. We also thank the Sandler Family Supporting Foundation for a Technology Award on the Zeiss 510 Multi-Photon microscope used in this study. In addition, we are grateful to the Mostov lab members for their input during the preparation of this manuscript. This investigation was supported by NIH grants to K.M.
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Vergés, M., Luton, F., Gruber, C. et al. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol 6, 763–769 (2004). https://doi.org/10.1038/ncb1153
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DOI: https://doi.org/10.1038/ncb1153
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