Glycosphingolipid-Protein Interaction in Signal Transduction.

Domenico Russo,Giovanni D’Angelo,Seetharaman Parashuraman

doi:10.3390/ijms17101732

Abstract

Glycosphingolipids (GSLs) are a class of ceramide-based glycolipids essential for embryo development in mammals. The synthesis of specific GSLs depends on the expression of distinctive sets of GSL synthesizing enzymes that is tightly regulated during development. Several reports have described how cell surface receptors can be kept in a resting state or activate alternative signalling events as a consequence of their interaction with GSLs. Specific GSLs, indeed, interface with specific protein domains that are found in signalling molecules and which act as GSL sensors to modify signalling responses. The regulation exerted by GSLs on signal transduction is orthogonal to the ligand–receptor axis, as it usually does not directly interfere with the ligand binding to receptors. Due to their properties of adjustable production and orthogonal action on receptors, GSLs add a new dimension to the control of the signalling in development. GSLs can, indeed, dynamically influence progenitor cell response to morphogenetic stimuli, resulting in alternative differentiation fates. Here, we review the available literature on GSL–protein interactions and their effects on cell signalling and development.

Highlights

Glycosphingolipids (GSLs) are a heterogeneous class of membrane lipids that are constituted by complex glycan moieties linked by a glycosidic bond to a ceramide lipophilic backbone [1]
We review some examples of GSL–protein interactions, and discuss their molecular aspects, their impact on the regulation of cell signalling, along with their pathophysiological significance
GSL synthesis starts in the endoplasmic reticulum (ER) where a sphingoid base is condensed with an acyl-CoA, to generate Ceramide (Cer) [102,103] (Figure 1)

Summary

Introduction

Glycosphingolipids (GSLs) are a heterogeneous class of membrane lipids that are constituted by complex glycan moieties linked by a glycosidic bond to a ceramide lipophilic backbone [1]. A number of studies have demonstrated that GSL-glycan moieties establish interactions with endogenous proteins or glycans located on the plasma membrane of the same or of neighbouring cells. The specificity of these interactions depends on the precise composition of GSL-glycan sugar residues [20,23,29,89,90,91]. Ganglioside with Neu5Acα2-3Galβ (Fucα1-3) GlcNAc epitope; nLc8, nLc10 and nLc12

GSL Synthesis and Turnover

GSL Regulation in Development

Which Are the Targets of GSL-Dependent Regulation?

How Is GSL Metabolism Regulated?

Which Is the Role of the GSL-Dependent Regulation in Development?