title: Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway.
abstract: MUC1 is a type I transmembrane glycoprotein aberrantly overexpressed in various cancer cells. It is thought to serve as a physical barrier from the extracellular environment and also as a receptor for various extracellular molecules. However, little is known about the fate of MUC1 during and after the interaction with these molecules. In the present study, we used anti-MUC1 antibody as an interacting molecule and investigated the cellular trafficking of MUC1. Our results showed that: (1) anti-MUC1 antibody was internalized only in MUC1 expressing cells and triggered internalization and down-regulation of MUC1; (2) the internalization of MUC1 by anti-MUC1 antibody required the cytoplasmic tail of MUC1 and was suppressed by inhibitors of Na(+)/H(+) exchanger, and caveola/raft-dependent internalization, but not by an inhibitor of clathrin-dependent internalization. We conclude that antibody-induced internalization of MUC1 involves the macropinocytotic pathway.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto 862-0973, Japan. hisatsun@kumamoto-u.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mikami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Kim
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010873:Pinocytosis; D021381:Protein Transport
chemical_list: D000911:Antibodies, Monoclonal; C060192:MUC1 protein, human; D018396:Mucin-1