Lipid rafts in neuronal signaling and function

doi:10.1016/S0166-2236(02)02215-4

Trends in Neurosciences

Volume 25, Issue 8, 1 August 2002, Pages 412-417

https://doi.org/10.1016/S0166-2236(02)02215-4 Get rights and content

Abstract

Lipid rafts are plasma membrane microdomains rich in cholesterol and sphingolipids, which provide a particularly ordered lipid environment. Rafts are enriched in glycosylphosphatidylinositol (GPI)-anchored proteins, as well as proteins involved in signal transduction and intracellular trafficking. In neurons, lipid rafts act as platforms for the signal transduction initiated by several classes of neurotrophic factors, including neurotrophins and glial-derived neurotrophic factor (GDNF)-family ligands. Emerging evidence also indicates that such rafts are important for neuronal cell adhesion, axon guidance and synaptic transmission. Thus, lipid rafts are structurally unique components of plasma membranes, crucial for neural development and function.

Section snippets

Neurotrophic factor signaling

The largest body of evidence indicating the significance of lipid rafts in neuronal function is in the realm of neurotrophic factor signaling. Most growth factors signal by binding to, and activating, receptor tyrosine kinases (RTKs) that autophosphorylate tyrosine residues, thereby creating binding sites for SH2 (Src homology 2)- and PTB (phosphotyrosine-binding)-domain containing proteins. These docking proteins form signaling complexes with activated RTKs that initiate multiple intracellular

Cell adhesion and axon guidance

Stable contacts between neurons and their targets are crucial for nervous system function. The regulation of these contacts by local and long-distance tropic and trophic factors is vital for axon guidance during development 41., 42., 43.. Growing evidence supports an important function of lipid rafts in these areas.

One observation that suggests that rafts are required for cell adhesion is that many adhesion molecules – such as TAG-1 (transiently expressed axonal glycoprotein-1), NCAM-120

Synaptic transmission

Recent studies have provided evidence that lipid rafts contribute to neuronal excitability. Two areas in which rafts contribute to synaptic transmission are in the clustering and regulation of neurotransmitter receptors and in the exocytotic process of neurotransmitter release.

Although some neurotransmitter receptors (e.g. the ionotropic glutamate receptor subunits NR1A [23] and GluR1 [53]) are not biochemically located in lipid rafts, other channels (e.g. the voltage-gated K^? channel Kv2.1 [54]

Conclusions

Compelling evidence is emerging from neural cells indicating the importance of lipid rafts in signal transduction and synaptic transmission. However, major questions remain regarding the exact role of rafts in the functioning of the nervous system. Cholesterol depletion, for example, is routinely used to disrupt rafts in cell membranes. However, treatments of this type also remove cholesterol from non-raft membranes and could have metabolic effects independent of raft disruption. An important

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Trends in Neurosciences

ReviewLipid rafts in neuronal signaling and function

Abstract

Section snippets

Neurotrophic factor signaling

Cell adhesion and axon guidance

Synaptic transmission

Conclusions

J. Biol. Chem.

Biochim. Biophys. Acta

Cell. Signal.

J. Biol. Chem.

J. Biol. Chem.

Immunity

Trends Cell Biol.

Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Neuron

Neuron

Curr. Opin. Neurobiol.

Curr. Opin. Neurobiol.

J. Biol. Chem.

Exp. Cell Res.

Cell

Cytokine Growth Factor Rev.

J. Biol. Chem.

FEBS Lett.

Cell

J. Biol. Chem.

Curr. Opin. Cell Biol.

Cell

Review
Lipid rafts in neuronal signaling and function