Membrane-bound transferrin-like protein (MTf): structure, evolution and selective expression during chondrogenic differentiation of mouse embryonic cells

Mouse membrane-bound transferrin-like protein (MTf) cDNA was cloned to exam ine its expression during chondrogenic differentiation in the mouse embryon ic cell line ATDC5, and to analyze the phylogenetic relationships among the MTfs of four animal species and 23 other transferrin members. Phylogenetic analysis indicated that the MTf gene diverged from the common ancestor gen e earlier than the genes of the other transferrins such as serum transferri n, lactoferrin and ovotransferrin, and that the divergence occurred after t he divergence of vertebrates and invertebrates. MTf, as well as the other t ransferrins, consists of two repeated domains. The similarity between the N -terminal and the C-terminal domains of MTf is much higher than that of the other transferrins, although the five amino acid residues required for iro n binding were not conserved in the C-terminal domain of MTf in contrast to the conservation of these residues in both domains of the other transferri ns. Among various adult mouse tissues, MTf mRNA was expressed at the highes t level in cartilage and at a moderate level in the testis. MTf mRNA was ex pressed only at very low levels in the brain, spleen, thymus, muscle, lung, skin and intestine, and hardly detected in the heart, kidney, stomach and liver. In cultures of the mouse ATDC5 cell line, MTf is developmentally exp ressed in parallel with the expression of type IT collagen and aggrecan, in the pattern commensurate with the onset of chondrogenesis to form cartilag e nodules. The structural characteristics and the expression pattern sugges t that during development and in adult tissues, MTf has some functions that are different from those of other transferrins. (C) 1999 Elsevier Science B.V. All rights reserved.