spektrin

Spectrin is a family of cytoskeletal proteins that lines the inner surface of the plasma membrane in many eukaryotic cells, most notably red blood cells, where it forms a mesh-like lattice that supports membrane integrity during deformation. It belongs to a larger spectrin family characterized by elongated, flexible polypeptides assembled from repeating spectrin domains.

In erythroid cells, spectrin forms alpha-beta heterodimers that assemble head-to-tail into tetramers. These tetramers associate with short actin filaments at junctional complexes to create a two-dimensional spectrin-actin network beneath the membrane. Linker proteins such as ankyrin bridge the spectrin lattice to transmembrane proteins (for example, band 3) and to the membrane, while other components like protein 4.1R stabilize the complex.

There are several spectrin family members with tissue-specific expression. Erythroid spectrin is highly enriched in red blood cells, imparting elasticity and resilience necessary for blood flow. Non-erythroid spectrins are found in neurons and other tissues and participate in membrane organization, cell polarity, and cytoskeletal interactions.

Functionally, the spectrin-based cytoskeleton provides mechanical support, maintains cell shape, and helps organize membrane domains. It also participates in cellular signaling and trafficking by coordinating the localization of membrane proteins and cytoskeletal elements during remodeling.

Clinical relevance: Reduced or abnormal spectrin expression or assembly can cause hereditary red blood cell membrane disorders, most notably hereditary spherocytosis and elliptocytosis, leading to hemolytic anemia. Mutations in non-erythroid spectrins have been associated with neurological disorders in some cases.