Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway

• Published in: Biochemical and biophysical research communications Vol. 388; no. 4; pp. 677 - 682
• Main Authors: Hisatsune, Akinori, Kawasaki, Mitsuru, Nakayama, Hideki, Mikami, Yuji, Miyata, Takeshi, Isohama, Yoichiro, Katsuki, Hiroshi, Kim, Kwang Chul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.10.2009
• Subjects: Anti-MUC1 antibody; Antibodies, Monoclonal - immunology; Cell Line; Cell Membrane - metabolism; Humans; Internalization; Macropinocytosis; MUC1; Mucin; Mucin-1 - genetics; Mucin-1 - immunology; Mucin-1 - metabolism; Pinocytosis; Protein Transport; MUC1; Mucin; Anti-MUC1 antibody; Internalization; Macropinocytosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.08.059

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.