A much broader scope of cellular functions of alpha-crystallin in lens is inferred from in vitro observations. Both alphaA and alphaB can bind specifically to actin, in vitro [13] and in vivo [14]. Although actin filament formation has been shown to be necessary for differentiation of lens epithelial cells [15], the significance of alpha-crystallin's interaction with actin in differentiation is not known. In the lens, alpha-crystallin also associates with type III intermediate filament proteins and the beaded filament proteins CP49 and CP115, and correct beaded filament assembly has been shown depend on the presence of alpha-crystallin [16]. Beaded filament mRNA levels are greatly increased in differentiating lens epithelium and have been suggested as a pan-specific marker for lens fiber development [17]. Alpha-crystallin has also been shown to interact directly with DNA [18]. In transfected CHO cells, alphaB has also been shown to ectopically localize to interphase nuclei, suggesting a role for this protein in the nucleus [19]. A nuclear role for alphaB in the lens was supported by the findings that a subset of lens epithelial cells derived from alphaB knockout mice demonstrated hyperproliferation and genomic instability [20]. In addition, the administration of exogenous alpha-crystallin to primary bovine lens epithelial cell cultures resulted in the formation of lentoid bodies, consistent with a role for these proteins in lens differentiation [21]. These findings indicate that alpha-crystallin may have a multitude of in vivo functions.