Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway.
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.
Hisatsune
Akinori
A
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto 862-0973, Japan. hisatsun@kumamoto-u.ac.jp
Kawasaki
Mitsuru
M
Nakayama
Hideki
H
Mikami
Yuji
Y
Miyata
Takeshi
T
Isohama
Yoichiro
Y
Katsuki
Hiroshi
H
Kim
Kwang Chul
KC
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
D000911:Antibodies, Monoclonal; C060192:MUC1 protein, human; D018396:Mucin-1