spectrin

Spectrin is a cytoskeletal protein family that forms a meshwork beneath the plasma membrane of most animal cells, most notably in red blood cells where it underpins membrane stability. Spectrin proteins are arranged as heterodimers of alpha- and beta-spectrin subunits. Two heterodimers associate head-to-head to form tetramers, creating a two-dimensional spectrin-actin network attached to the membrane via ankyrin and actin-binding proteins. This network supports cell shape, provides elasticity, and organizes membrane domains.

Many spectrin isoforms exist. The best-studied are alpha-spectrin and beta-spectrin; alpha-spectrin is encoded by SPTA1 (erythroid) and SPTAN1 (non-erythroid), while beta-spectrin includes SPTB and SPTBN1–SPTBN4. Neuronal isoforms such as alpha II-spectrin and beta III-spectrin contribute to the cytoskeletal architecture of axons, dendrites, and synapses, and beta-spectrins participate in the composition of the axon initial segment and nodes of Ranvier by interacting with ankyrin-G and voltage-gated channels.

Spectrin repeats, elongated helical motifs in spectrin subunits, facilitate flexible yet sturdy connections with actin, ankyrin, and membrane proteins such as Band 3.

Clinical relevance: Mutations or deficiency in spectrin can cause hereditary spherocytosis, a hemolytic anemia resulting from fragile red blood cells. Other spectrin-related disorders include neurodevelopmental and spinocerebellar ataxias associated with specific isoforms.

In summary, spectrin is a core component of the membrane skeleton that coordinates mechanical stability, membrane organization, and signaling across diverse cell types.