Bone Morphogenetic Proteins (BMPs) exhibit multiple functions during development. They are assumed to play signaling roles in the mediation of epithelio-mesenchymal interactions during tooth development and repair. This review aims to survey the hitherto data on BMPs during tooth development with an attempt to stress a possible functional relationship between epithelial BMPs expression and regressive processes representing integral part of normal odontogenesis. During tooth development, BMPs gene transcription appears to be involved in early condensation and further differentiation of the dental mesenchyme and of its derivatives. The expression of BMPs transcripts in the dental epithelium, however, is specifically restricted both in space and time during prenatal development. In mouse, these sites of BMP-2, BMP-4 and BMP-7 transcripts mostly fit with the areas, where apoptosis has been reported during reduction or even elimination of specific dental epithelial cell populations: i. rudimental tooth primordia in the prospective mouse diastema, ii. the enamel knot, iii. ameloblasts, iv. the residual dental lamina (gubernaculum of the enamel organ). These data strongly suggest involvement of the BMP-4 in upregulation of apoptosis also during odontogenesis. A possible implication of other BMPs and their precise role in regressive processes should be investigated.
The compartmentation of glycosyltransferases in specific cisternae of the Golgi apparatus can control their access to glycoconjugate substrates and sugar nucleotide donors and thus the types of oligosaccharide structures made by the cell. With an interest in compartmentation as a way of controlling glycosyltransferase activity, as well as a general interest in how proteins are localized in the Golgi, several investigators have been studying the signals and mechanisms that direct glycosyltransferase Golgi localization. After several years of research, many aspects of this complicated process still remain a mystery. It is now clear that some proteins, like the β1, 4-galactosyltransferase, may use their transmembrane domains as their primary Golgi retention signals, while other proteins, like the N-acetylglucosaminyltransferase I and α2, 6-sialyltrans-ferase, either require both lumenal and transmembrane domains for efficient Golgi retention and/or possess more than one domain that functions as an independent retention region. The role of cytoplasmic sequences in Golgi retention is still controversial and new evidence suggests that we cannot discount these sequences in the Golgi retention process. Based on the variety of sequences required for Golgi retention, two potential mechanisms have been hypothesized. The first of these is the bilayer thickness mechanism of Golgi retention and is based on the fact that the transmembrane domains of many Golgi proteins play important roles in their localization. The second of these is the oligomerization/kin recognition mechanism of Golgi retention which can be used to explain the requirement for non-transmembrane sequences or multiple domains in the Golgi retention process. The evidence supporting these mechanisms, how they could work together to effect Golgi retention, and future directions in this area are discussed.
Sialic acids are abundant on the surface of mammalian cells where, through their negative charge, they assist in the prevention of undesirable cell-cell interactions. The recent discovery of the sialoadhesin subset of the immunoglobulin superfamily, which includes sialoadhesin, CD22, myelin associated glycoprotein (MAG) and CD33, has raised the possibility that sialic acids are also instrumental in promoting cell-cell interactions in a variety of physiological systems. Each of these membrane proteins exhibits a distinct specificity for both the type of sialic acid recognised and its linkage to subterminal sugars. They share a high degree of sequence similarity within the NH2-terminal two Ig domains which also display a unique arrangement of conserved disulphide bonds. Domains 1 and 2 (numbering from the NH2-terminus) are likely to be representative of an ancestral gene that gave rise to the current members of the family through gene duplication. By generating truncated recombinant proteins, together with site-directed mutagenesis, the GFCC′C″ faces of the NH2 terminal V-set domains of sialoadhesin and CD22 have been shown to contain the sialic acid binding site. Recently, this has been confirmed by X-ray crystallography which has led to the structural determination of the V-set domain of sialoadhesin complexed with a ligand, 3′ sialyllactose. The similarities and differences in sialic acid recognition by sialoadhesin and other sialic acid binding proteins are discussed.