Spectrins
spectrins
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. The protein is named spectrin since it was first isolated as a major protein component of human red blood cells which had been treated with mild detergents; the detergents lysed the cells and the hemoglobin and other cytoplasmic components were washed out. In the light microscope the basic shape of the red blood cell could still be seen as the spectrin containing submembranous cytoskeleton preserved the shape of the cell in outline. This became known as a red blood cell 'ghost', and so the major protein of the ghost was named spectrin. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure. The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh.  In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain, destroying the cytoskeleton. Spectrin cleavage causes the membrane to form blebs and ultimately to be degraded, usually leading to the death of the cell. Spectrin subunits may also be cleaved by caspase family enzymes, and calpain and caspase produce different spectrin breakdown products which can be detected by western blotting with appropriate antibodies. Calpain cleavage may indicate activation of necrosis, while caspase cleavage may indicate apoptosis.