Regulation of Plasma Membrane Supramolecular Functional Units by Late Endosomal Sorting and Transport
Cellular membranes segregate into local ordered microdomains (“rafts”), physical units which assemble and interconnect cooperating molecules and serve as plasma membrane signaling hubs. In particular, tetraspanin-enriched microdomains (TEM) have been implicated in adhesion events occurring during migration and invasion, in leukocyte extravasation, host/pathogen interaction, and in various signaling pathways. The plasma membrane in general and the tetraspanin-enriched microdomains in particular undergo dynamic rearrangements due to both constant and regulated endo- and exocytotic events, the impact of which is often underestimated. We have recently identified a novel layer of regulation for TEM-controlled cell surface processes that is exerted from endosomal compartments. Based on our findings, we hypothesize that late endosomes act as a tetraspanin reservoir and that complex TEM-based cellular functions at the plasma membrane (e.g. in leukocyte recruitment) are affected by tetraspanin trafficking from late endosomes to the plasma membrane. The goal of the project is to gain information on the biological significance of tetraspanin recruitment to late endosomes. We will link changes of late endosomal tetraspanin levels to functional TEM alterations at the cell surface, and we will unravel the molecular mechanisms whereby tetraspanins are directed from late endosomes to the plasma membrane.