title: Truncation of betaA3/A1-crystallin during aging of the bovine lens; possible implications for lens optical quality.
abstract: During aging, extensive modifications of eye lens proteins take place, which may contribute to the development of cataract. Truncation of the accessible extensions of beta-crystallins has been suggested to be an important factor in this process. We therefore studied the truncations of bovine betaA3- and betaA1-crystallin in more detail. These proteins are identical except for the length of their N-terminal extension, 30 and 13 residues, respectively. The water-soluble and -insoluble proteins from cortex and nucleus of bovine lenses of different ages were separated by 2D-gel electrophoresis and immuno-blotted with an antiserum against betaA3. Two major truncation products were detected, which by sequence analysis were found to correspond to betaA3 having lost 11 or 22 amino acids. betaA3(-11) was only observed in the nucleus, whereas betaA3(-22) was present both in cortex and nucleus. We argue, therefore, that each of these two products is produced by a separate proteolytic enzyme. betaA3(-22) can originate by cleavage of betaA3, betaA1 and betaA3(-11). Truncation of betaA3 occurs more readily than that of betaA1, while betaA3(-11) disappears at an intermediate rate. It appears that the longer the N-terminal extension, the easier proteolysis takes place. Truncated proteins are not necessarily prone to end up in the water-insoluble fractions; other modifications leading to charge changes are more likely to be responsible for insolubilization. Truncation of the extensions of beta-crystallins could be a functional rather than a harmful process during aging of the lens; by modulating protein repulsion, it may help to maintain the protein concentration gradient that is necessary for the optical quality of the lens.
authors.affiliation: Department of Biochemistry, University of Nijmegen, P.O. Box 9101, Nijmegen, HB, 6500, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Werten
authors.forename: E
authors.initials: E
authors.lastname: Vos
authors.forename: W W
authors.initials: WW
authors.lastname: De Jong
mesh_terms: D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D002386:Cataract / Q000378:metabolism / Q000503:physiopathology; D002417:Cattle; D003459:Crystallins / Q000096:biosynthesis*; D005136:Eye Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008969:Molecular Sequence Data; D012029:Refraction, Ocular / Q000502:physiology; D014792:Visual Acuity / Q000502:physiology