Lipid rafts, protein scaffold and neurologic disease

Benarroch EF. Neurology 2007; 69: 1635-1639.

Review article. Lipid rafts are specialized microdomains of the plasma membrane involved in vesicular transport and signalling mechanisms. They are encoded in cholesterol, sphingolipids, and scaffolding prteins such as caveolins and septins. Mutation of caveolin-3 is associated with diverse muscle disorders. Lipid rafts may be the site of abnormal processing of APP and prion protein.. Impaired septin-4 function can lead to synuclein accumulation and neurotoxicity in Parkinson's disease.

Lipid rafts are also characterized by their interactions with the cytoskeleton. Caveolin and flotillin act as scaffolding proteins that recruit signalling proteins into lipid rafts. Cholesterol depletion disrupts lipid rafts, leading to decreased accunulation and uptake of glutamate, GABAm or serotonin transporters. Caveolin 3 colocalizes with dysferlin. Mutations of CAV# are linked to limb girdle dystrophy 1C, rippling muscle disease, hyperCKEemia, distal myopathy, and a recessive form of LGD. Septin 4 is a component of the presynaptic scaffold in dopaminergic neurons projecting to the striatum.