Spectrins in human diseases

Abstract

Spectrin is one of the major components of a plasma membrane-associated network, known as the spectrin-based skeleton. The spectrin-dependent skeleton was first identified at the membrane of human erythrocytes, the best known membranes in terms of structure, function, and genetic disorders. Mutations in genes encoding erythroid spectrins cause hemolytic anemia such as hereditary elliptocytosis and hereditary spherocytosis. Present in all mammalian cells, spectrins, and the spectrin-based skeleton are required for organization of specialized membrane domains. Recent advances reveal that these proteins actively participate in cellular localization of a surprisingly diverse set of proteins in many cell types. Recent studies, such as the description of nonerythroid spectrin defects in cerebellar ataxia, lead to an emerging concept for pathogenesis of human disease where failure in cellular localization of membrane proteins results in loss of physiological function.