Lipid Rafts and Bullous Diseases

Abstract

Multiple observations point to involvement of lipid membrane domains, known as lipid rafts, in the pathology of human disorders. The putative role of lipid rafts in hereditary and acquired skin blistering diseases is discussed in this review. Stable adhesion of the epidermis to the underlying basement membrane is secured by hemidesmosomes, specialized multiprotein complexes in basal keratinocytes. Loss of function of hemidesmosomal proteins due to inherited or acquired abnormalities result in weak dermal-epidermal adhesion and blistering of the skin. Lipid rafts regulate biological functions of two hemidesmosomal transmembrane components: collagen XVII and α6β4 integrin. Ectodomain shedding of collagen XVII is regulated by membrane lipid domains, suggesting involvement of lipid rafts in the pathogenesis of junctional epidermolysis bullosa, a genetic disease caused by mutations in the collagen XVII gene, and of bullous pemphigoid, an autoimmune disease with autoantibodies to this collagen. Similarly, adhesive and signaling functions of α6β4 integrin are modulated by lipid rafts, again linking lipid rafts to junctional epidermolysis bullosa. Therefore, modulation of lipid domains in the epidermis might have therapeutic potential for this group of skin blistering diseases.