Regulation of αA- and αB-crystallins via phosphorylation in cellular homeostasis

alpha A-Crystallin (alpha A) and alpha B-crystallin (alpha B) are small heat shock proteins responsible for the maintenance of transparency in the lens. In non-lenticular tissues, alpha B is involved in both maintenance of the cytoskeleton and suppression of neurodegeneration amongst other roles. Despite their importance in maintaining cellular health, modifications and mutations to alpha A and alpha B appear to play a role in disease states such as cataract and myopathies. The list of modifications that have been reported is extensive and include oxidation, disulphide bond formation, C- and N-terminal truncation, acetylation, carboxymethylation, carboxyethylation, carbamylation, deamidation, phosphorylation and methylation. Such modifications, notably phosphorylation, are alleged to cause changes to chaperone activity by inducing substructural changes and altering subunit exchange dynamics. Although the effect modification has on the activities of alpha A and alpha B is contentious, it has been proposed that these changes are responsible for the induction of hyperactivity and are thereby indirectly responsible for protein deposition characteristic of many diseases associated with alpha A and alpha B. This review compiles all reported sites of alpha A and alpha B modifications, and investigates the role phosphorylation, in particular, plays in cellular processes.