Constitutive internalization of murine MHC class I molecules
Article first published online: 16 OCT 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 210, Issue 2, pages 445–455, February 2007
How to Cite
Mahmutefendić, H., Blagojević, G., Kučić, N. and Lučin, P. (2007), Constitutive internalization of murine MHC class I molecules. J. Cell. Physiol., 210: 445–455. doi: 10.1002/jcp.20877
- Issue published online: 22 NOV 2006
- Article first published online: 16 OCT 2006
- Manuscript Accepted: 17 AUG 2006
- Manuscript Received: 15 APR 2006
- Ministry of Science, Education and Sports of the Republic of Croatia. Grant Numbers: 062006, 0062030
The total number of cell surface glycoprotein molecules at the plasma membrane results from a balance between their constitutive internalization and their egress to the cell surface from intracellular pools and/or biosynthetic pathway. Constitutive internalization is net result of constitutive endocytosis and endocytic recycling. In this study we have compared spontaneous internalization of murine major histocompatibility complex (MHC) class I molecules (Kd, Dd, full Ld, and empty Ld) after depletion of their egress to the cell surface (Cycloheximide [CHX], brefeldin A [BFA]) and internalization after external binding of monoclonal antibody (mAb). MHC class I alleles differ regarding their cell surface stability, kinetics, and in the way of internalization and degradation. Kd and Dd molecules are more stable at the cell surface than Ld molecules and, thus, constitutively internalized more slowly. Although the binding of mAbs to cell surface MHC class I molecules results in faster internalization than depletion of their egress, it is still slow and, thereby, can serve as a model for tracking of MHC class I endocytosis. Internalization of fully conformed MHC class I molecules (Kd, Dd, and Ld) was neither inhibited by chlorpromazine (CP) (inhibitor of clathrin endocytosis), nor with filipin (inhibitor of lipid raft dependent endocytosis), indicating that fully conformed MHC class I molecules are internalized via the bulk pathway. In contrast, internalization of empty Ld molecules was inhibited by filipin, indicating that non-conformed MHC class I molecules require intact cholesterol-rich membrane microdomains for their constitutive internalization. Thus, conformed and non-conformed MHC class I molecules use different endocytic pathways for constitutive internalization. J. Cell. Physiol. 210: 445–455, 2007. © 2006 Wiley-Liss, Inc.