alphaspectrin

Alphaspectrin (also written α‑spectrin) is a cytoskeletal protein belonging to the spectrin family, which provides structural support and flexibility to the plasma membrane of eukaryotic cells. It is a heterodimer composed of an α‑spectrin subunit and a β‑spectrin partner, forming a flexible, rod‑shaped molecule that links actin filaments to membrane proteins such as ankyrin and band 3. In vertebrates, the α‑spectrin isoform is encoded by the SPTA1 gene and is expressed in a variety of tissues, with particularly high abundance in erythrocytes, neurons, and muscle cells.

The primary function of alphaspectrin is to maintain membrane integrity during mechanical stress. In red blood cells, the αβ‑spectrin tetramer forms a lattice beneath the lipid bilayer, allowing the cell to deform while traversing capillaries and then recover its shape. In neurons, α‑spectrin contributes to the organization of the axonal membrane, supporting the formation of the periodic actin‑spectrin skeleton that regulates ion channel distribution and axonal transport.

Alphaspectrin was first identified in the early 1970s through biochemical fractionation of erythrocyte membranes, and its gene was cloned in the 1990s. Mutations in SPTA1 are associated with hereditary spherocytosis, a hemolytic anemia characterized by fragile, spherical red cells, and with certain neurodevelopmental disorders where spectrin defects disrupt axonal architecture.

Research on alphaspectrin explores its role in membrane repair, mechanotransduction, and cellular signaling. Therapeutic strategies under investigation aim to correct spectrin deficiencies using gene editing or protein‑replacement approaches. The protein also serves as a biomarker for membrane integrity in studies of blood storage and transfusion medicine. Current literature continues to elucidate the diverse physiological and pathological contexts in which alphaspectrin functions.