Glycolipids and Lectins in Endocytic Uptake Processes

A host of endocytic processes has been described at the plasma membrane of eukaryotic cells. Their categorization has most commonly referenced cytosolic machinery, of which the clathrin coat has occupied a preponderant position. In what concerns intra-membrane constituents, the focus of interest has been on phosphatidylinositol lipids and their capacity to orchestrate endocytic events on the cytosolic leaflet of the membrane. The contribution of extracellular determinants to the construction of endocytic pits has received much less attention, depite the fact that (glyco)sphingolipids are exoplasmic leaflet fabric of membrane domains, termed rafts, whose contributions to predominantly clathrin-independent internalization processes is well recognized. Furthermore, sugar modifications on extracellular domains of proteins, and sugar-binding proteins, termed lectins, have also been linked to the uptake of endocytic cargoes at the plasma membrane. In this review, we first summarize these contributions by extracellular determinants to the endocytic process. We thus propose a molecular hypothesis - termed the GL-Lect hypothesis - on how GlycoLipids and Lectins drive the formation of compositional nanoenvrionments from which the endocytic uptake of glycosylated cargo proteins is operated via clathrin-independent carriers. Finally, we position this hypothesis within the global context of endocytic pathway proposals that have emerged in recent years.