Structural and functional studies of galectin-1: a novel axonal regeneration-promoting activity for oxidized galectin-1.
Recently, we discovered oxidized galectin-1 as a factor that regulates initial axonal growth in the peripheral nerve after axotomy. Galectin-1 is a member of the galectins, a family of animal lectins ranging from Caenorhabditis elegans to humans, which is defined by their affinity for beta-galactosides and by significant sequence similarity in the carbohydrate-binding site. Galectin-1 is a homodimer with a subunit molecular mass of 14.5 kDa, which contains six cysteine residues per subunit. The cysteine residues should be in a free state in order to maintain a molecular structure that is capable of showing lectin activity. However, our structural analysis revealed that the axonal regeneration-promoting factor exists as an oxidized form of galectin-1, containing three intramolecular disulfide bonds. The oxidized galectin-1 exhibited marked peripheral nerve regeneration-promoting activity, although it showed no lectin activity. It was also revealed that oxidized galectin-1 exists as a monomer in a physiological solution. Galectin-1 seems to have a variety of biological functions. These functions could vary according to the time at which a biological function is taking place, as well as the site in which a biological function is taking place. In addition, these functions could vary according to the structure of galectin-1 by which a particular biological function is taking place. Disulfide bond formation alters the structure of galectin-1, so as to confer the novel ability to promote axonal regeneration. Oxidized galectin-1 likely acts as an autocrine or paracrine factor to promote axonal regeneration, functioning more like a cytokine than as a lectin.
Kadoya
Toshihiko
T
CMC R&D Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., Takasaki, Gunma, Japan. tkadoya@kirin.co.jp
Horie
Hidenori
H
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D037483:Galectin 1 / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009416:Nerve Regeneration; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D037483:Galectin 1