The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor.
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 lifespan. The polymeric immunoglobulin receptor (pIgR) transcytoses polymeric IgA (pIgA) from the basolateral to the apical surface of epithelial cells and hepatocytes. 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 enzymes. The yeast retromer contains two sub-complexes. One includes the Vps5p and Vps17p subunits, which provide mechanical force for vesicle budding. The other is the Vps35p-Vps29p-Vps26p subcomplex, which provides cargo specificity. The mammalian retromer binds to the mannose 6-phosphate receptor, which sorts lysosomal enzymes from the trans-Golgi network to the lysosomal pathway. Here, we show a function for the mammalian Vps35-Vps29-Vps26 retromer subcomplex in promoting pIgR-pIgA transcytosis.
Vergés
Marcel
M
Department of Anatomy, University of California, San Francisco, CA 94143-2140, USA.
Luton
Frédéric
F
Gruber
Carmen
C
Tiemann
Frank
F
Reinders
Lorri G
LG
Huang
Lan
L
Burlingame
Alma L
AL
Haft
Carol R
CR
Mostov
Keith E
KE
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016764:Cell Polarity; D003902:Detergents / Q000494:pharmacology; D004285:Dogs; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007150:Immunohistochemistry; D011233:Precipitin Tests; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*
D003902:Detergents; D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; C034639:polymeric IgA