Glycolipids and Lectins in Endocytic Uptake Processes

Abstract

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 the intramembrane 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, despite the fact that (glyco)sphingolipids are exoplasmic leaflet fabric of membrane domains, termed rafts, whose contributions to predominantly clathrin-independent internalization processes are well recognized. Furthermore, sugar-binding proteins, termed lectins, and sugar modifications on extracellular domains of proteins have also been linked, have also been linked to the uptake of endocytic cargos at the plasma membrane. In this review, we 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 nanoenvironments 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 the recent years.