Abstract
Gangliosides have been shown to modulate various growth factor receptors such as epidermal growth factor receptor (EGFR), insulin receptor (IR), platelet derived growth factor receptor (PDGFR), neural growth factor receptor (NGFR) and fibroblast growth factor receptor (FGFR). Although traditional data obtained by exogenous addition of gangliosides into culture medium suggested that gangliosides are involved in various cellular functions as coordinators of multiple receptor functions, the molecular mechanisms underlying these phenomena were remained unknown. Recent studies show that the presence of membrane microdomains (lipid raft) highly enriched in cholesterol and glycosphingolipids (GSL), but lacking in phospholipids. Within the past decade, data have emerged from many laboratories implicating these lipid microdomains as critical for proper compartmentalization of growth factor signaling. In this review, we will summarize these observations and discuss a new concept ganglioside-mediated regulation of growth factor receptors in microdomains. How gangliosides and growth factor receptors are related to diseases? Here, we present evidence of a new pathological feature of insulin resistance in adipocytes caused by dissociation of IR-caveolin-1 complex by ganglioside GM3 in microdomains.
