Nature Cell Biology
6, 763 - 769 (2004)
Published online: 11 July 2004; | doi:10.1038/ncb1153
The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptorMarcel Vergés1, Frédéric Luton1, 2, Carmen Gruber3, Frank Tiemann3, Lorri G. Reinders4, Lan Huang4, Alma L. Burlingame4, Carol R. Haft5
& Keith E. Mostov11
Department of Anatomy, and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2140, USA. 2
Present address: Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-UMR6097, 06560 Sophia-Antipolis, France. 3
Atugen AG, D-13125 Berlin, Germany. 4
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-0446, USA. 5
Division of Diabetes, Endocrinology and Metabolic Diseases, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-5460, USA.
Correspondence should be addressed to Keith E. Mostov mostov@itsa.ucsf.eduEpithelial 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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