Protein 4.1, a multifunctional protein of the erythrocyte membrane skeleton: structure and functions in erythrocytes and nonerythroid cells.

Protein 4.1 of red blood cells (4.1R) is a multifunctional protein essential for maintaining erythrocyte shape and membrane mechanical properties, such as deformability and stability, through lateral interactions with spectrin and actin in the skeletal network and vertical interactions with cytoplasmic domains of transmembrane proteins, glycophorin C, and band 3. The primary stucture of the major 80-kd isoform of 4.1R has been elucidated, and on the basis of this identification, the functional domains and sites for binding partners have been clarified. Posttranslational modification of 4.1 R, such as phosphorylation and proteolysis, as well as binding of regulatory proteins including calmodulin-Ca2+ to 4.1R, modulates its interactions with other membrane proteins and, consequently, the membrane functions of red blood cells. Alternative splicing occurs in the 4.1R gene, and various isoforms are expressed not only in erythroid but also in nonerythroid cells. This review introduces current knowledge on biochemical, biophysical, genetic, and functional aspects of 4.1R and its family proteins, 4.1G (general type), 4.1B (brain type), and 4.1N (neuron type), recently identified in nonerythroid cells.