Metabolism of Glycolipids at the Cell Surface

JOSE L. DANIOTTI; A. ALEJANDRO VILCAES; MACARENA RODRIGUEZ-WALKER; FERNANDO M. RUGGIERO

Sphingolipids: Biology, Synthesis and Functions

Nova Science Publishers Inc

Año: 2015; p. 67 - 90

Glycosphingolipids (GSLs) are amphipathic molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are mono- or multi-sialosylated GSLs ubiquitously distributed on the external leaflet of vertebrate plasma membranes. Gangliosides have been implicated in many physiological processes, including growth, apoptosis, cell adhesion and endocytosis, as well as in pathological processes due to their capacity to function as receptors for several toxins, viruses and antibodies. Their de novo synthesis starts at the endoplasmic reticulum and continues by a combination of glycosyltransferase activities at the Golgi complex, followed by vesicular delivery to the plasma membrane. At the cell surface, gangliosides can undergo endocytosis, and once internalized they can be sorted in a cell-type-dependent manner into endosomes for recycling to the plasma membrane or to be catabolized at the lysosomal level. However, a number of enzymes for ganglioside anabolism and catabolism have recently been shown to associate with the plasma membrane, being able to exert their enzymatic activities on substrates residing in the same surface (cis-catalytic activity) and in that of neighboring cells (trans-catalytic activity). The action of these enzymatic activities may be responsible for structural changes of the plasma membrane gangliosides, thus modifying membrane organization, and consequently, different signaling processes. In this Chapter, we review early and recent advances concerning the glycolipid metabolism at the cell surface, as well as its possible biological implications, which represents a new paradigm in the cellular control of glycolipid expression.