engleski

Early endosomal rerouting of major histocompatibility class I conformers

Major histocompatibility class I (MHC-I) molecules are present at the cell surface both as fully conformed trimolecular complexes composed of heavy chain, beta-2-microglobulin and peptide, and various open forms, devoid of peptide and/or beta-2-microglobulin (open MHC-I conformers). Fully conformed MHC-I complexes and open MHC-I conformers can be distinguished by well characterized monoclonal antibody reagents that recognize their conformational difference in the extracellular domain. In the present study we used these tools in order to test whether conformational difference in the extracellular domain determines endocytic and endosomal route of plasma membrane proteins. We analyzed plasma membrane localization, internalization, endosomal trafficking and recycling of human and murine MHC-I proteins on various cell lines. We have shown that fully conformed MHC-I and open MHC-I conformers segregate at the plasma membrane and during endosomal trafficking resulting in the exclusion of open MHC-I conformers from the recycling route. This segregation is associated with their partitioning into the membranes of different compositions. As a result, the open MHC-I conformers internalized with higher rate than fully conformed counterparts. Thus, our data suggest the existence of conformation-based protein sorting mechanism in the endosomal system.

Endocytosis; Early endosomes; Endosomal recycling; Major Histocompatibility Class I proteins; Open MHC-I conformers

nije evidentirano