Biological Implication of the Membrane Rafts in Neuronal Cells

Previous studies have suggested that caveolae, glycosphingolipid- and cholesterol-enriched microdomains, or lipid rafts, within the plasma membrane of eukaryotic cells are implicated in many important cellular events, such as polarized sorting of apical membrane proteins in epithelial cells and signal transduction. Until recently, however, the existence of such domains in vivo remained controversial. The past few years have brought compelling evidence that microdomains indeed exist in living cells. These special membrane structures have a very unusual polarity in their enrichment of sphingolipids such as ganglioside GM1 (GM1), sphingomyelin, cholesterol, and signaling molecules such as receptor-type tyrosine kinase, G proteins, glycophosphatidylinositol-anchored proteins such as c-Src. In the nervous system, however, these membrane structures have been scarcely investigated, although the neuron is the most attractive and the greatest challenge to research on membrane traffic and function. An increasing body of evidence has suggested that neurotrophic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3/4 (NT-3/4) are actually involved in the process of neuronal differentiation, survival, and synaptic plasticity. Recent studies including ours have suggested that the receptors for these neurotrophic factors, Trk-family tyrosine kinase, are present in these special membrane structures and they modulate these Trk-family tyrosine kinase functions. In this review, I will focus on the current understanding of the structure and the function of these special membrane microdomains in neuronal cells, especially their action on the cellular signaling events.