A Retinaldehyde Dehydrogenase as a Structural Protein in a Mammalian Eye Lens

Abstract

-Crystallin is a taxon-specific crystallin, a major component of the eye lens in elephant shrews (Macroscelidea). Sequence analysis of -crystallin from two genera of elephant shrews and expression of recombinant -crystallin show that the protein is a cytoplasmic (class 1) aldehyde dehydrogenase (ALDH1, EC 1.2.1.3) with activity for the oxidation of retinaldehyde to retinoic acid. Unlike many other mammals, elephant shrews have two ALDH1 genes. One encodes ALDH1/-crystallin which, in addition to its very high expression in lens, is also the predominant form of ALDH1 expressed in other parts of the eye. The second gene encodes a "non-lens" ALDH1 (ALDH1-nl) which is the predominant form expressed in liver. This pattern of tissue preference contrasts with other mammals which make use of the same major ALDH1 transcript in both ocular and non-ocular tissues. Thus the gene recruitment of ALDH1/-crystallin as a structural protein in elephant shrew lenses is associated with its collateral recruitment as the major form of ALDH1 expressed in other parts of the eye.

Xenopus Cytosolic Thyroid Hormone-binding Protein (xCTBP) Is Aldehyde Dehydrogenase Catalyzing the Formation of Retinoic Acid

“…This discrepancy suggests the possibility of posttranscriptional or -translational regulation, or some other form of modulation of T 3 binding activity of xCTBP. Dual functional properties of ALDH1 have also been reported for other species, such as for elephant shrew (23) and giant octopus crystallins as major component of lens proteins (see Fig. 3) and human 56-kDa androgen-binding protein in genital skin fibroblast (24).…”

“…This analysis supports the specific branching orders for the major groups, which are ((ALDH6, ALDH1) and (ALDH5, ALDH2)), ALDH9) as shown in the tree by Yoshida et al (62). Proteins with catalytic activity converting retinal to RA are indicated by asterisks (20,22,23,38,39,45,(52)(53)(54)(55)57 …”

Structurally Normal Corneas in Aldehyde Dehydrogenase 3a1-Deficient Mice

“…An example of the latter is gelsolin in zebrafish cornea (49). Accumulation of ALDH in mammalian corneas is of interest, since -crystallin of the elephant shrew lens (15) and ⍀-crystallin of the cephalopod (28,45,50) and scallop (36) lenses are also members of the ALDH family. Further experiments are required to determine the roles for the different, abundant, water-soluble proteins in the cornea, including ALDH3a1 in the mouse and other mammals.…”

“…These include gelsolin in zebrafish, isocitrate dehydrogenase in cow, cyclophilin in chicken, and glutathione S-transferase homologues in squid (33,43,49). Among these, the mammalian ALDH3a1 represents a particularly interesting comparison to lens crystallins, since it is a known abundant corneal enzyme that has family members, -crystallin and ⍀-crystallin, represented among the lens crystallins (15,28,36,45,50).…”

Genome-scale identification and characterization of moonlighting proteins

“…Crystallins in several mammals, geckos, birds, and some other species are eye lens proteins that retain their metabolic functions, including lactate dehydrogenase, arginosuccinate lyase, and α-enolase [5][6][7][8]. Many known moonlighting proteins were originally recognized as enzymes, but there are also others that were known as receptors, channel proteins, chaperone proteins, ribosomal proteins, and scaffold proteins [1,9,10].…”