Lipid raft microdomains and neurotransmitter signalling

Key Points Lipid rafts are submicroscopic membrane microdomains rich in sphingomyelin and cholesterol. Two common types of lipid raft have been proposed and studied in neurotransmitter signalling: planar lipid rafts (also known as non-caveolar, or glycolipid, rafts) and caveolae. Several classes of neurotransmitter receptors and transporters associate with lipid raft membrane domains and the functional effects of this association are heterogeneous. Lipid rafts are involved in the clustering and trafficking of receptors and transporters, and these rafts seem to be capable of either facilitating or inhibiting neurotransmitter signalling or transport. Cytoskeletal elements such as microtubules or actin microfilaments, and the monomers or dimers that comprise them, associate with lipid rafts and might function to orchestrate neurotransmitter signalling. The localization of signalling components to lipid rafts indicates that molecular events altering this association could contribute to a number of neurological or psychiatric diseases. The heterogeneous action of lipid rafts on neurotransmitter signalling might help to form a uniform hypothesis for the role played by these domains and could help point the way to a mechanism whereby manipulation of rafts generates a pattern of altered information flow. Lipid rafts — specialized plasma membrane microdomains that are thought to regulate various signalling events — are the focus of intensive research into their roles in the nervous system. Here, Rasenick and colleagues review the evidence for their involvement in regulating neurotransmitter signalling. Lipid rafts are specialized structures on the plasma membrane that have an altered lipid composition as well as links to the cytoskeleton. It has been proposed that these structures are membrane domains in which neurotransmitter signalling might occur through a clustering of receptors and components of receptor-activated signalling cascades. The localization of these proteins in lipid rafts, which is affected by the cytoskeleton, also influences the potency and efficacy of neurotransmitter receptors and transporters. The effect of lipid rafts on neurotransmitter signalling has also been implicated in neurological and psychiatric diseases.