The Cerebroside Sulfate Activator (CS-Act) is a small protein involved in the catabolism of cerebroside sulfates (sulfatides) and a number of other glycosphingolipids. It is also commonly referred to as SAP-1 or Saposin B. CS-Act is believed to function by binding target lipids, extracting them from membranes or micelles and making them available to water soluble enzymes. The protein probably also plays a role in intermembrane transport of these lipids. The protein is noted for exceptional thermal and proteolytic stability and a multi-amphipathic helix bundle structure stabilized by internal disulfides has been proposed. CS-Act is defective in a rare form of Metachromatic Leukodystrophy and the responsible mutations have been defined. The CS-Act protein is derived from a much larger precursor, Prosaposin, which gives rise to a family of structurally similar proteins believed to have related biochemical activities. The relative abundance of CS-Act, the other Saposins and Prosaposin, as well as the anatomic and developmental profiles of these proteins and their messenger RNA suggests that they may play more profound biological roles than originally envisioned.

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The cellular stress response is a model for the regulation of gene expression and represents a highly conserved mechanism for cells that respond to a changing environment. The cellular stress response includes a significant glycobiological component, which although not well characterized, appears essential and complementary to the role of“classical” heat shock proteins (HSPs). This review concentrates on the glycobio-logical component of the mammalian stress response, where several major heat stress-induced glycoproteins have been identified to date. For example, the expression and glycosylation of GP50 and GP62 is associated with the development of thermotolerance, while P-SG67 and P-SG64 are glycosylated “promptly”, i.e., within minutes after the initiation of heat stress. GP50 in CHO cells is homologous to the serpin family-related retinoic acid-inducible mouse J6 gene product, whereas P-SG67 and P-SG64 are glycosylated variants of the multifunctional ER protein, calreticulin. Potential functions for stress glycoproteins and their possible interaction with HSPs are discussed. The availability of molecular probes for stress glycoproteins should facilitate studies to understand their functions and to utilize them in biotechnological applications.

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Cell adhesion molecules (CAM) play key roles in the fundamental processes of growth and development, particularly in the nervous system. This review focuses on the evidence implicating the cadherin, integrin and immunoglobulin superfamily of cell adhesion molecules in various signal transduction pathways. In addition to modulating cell adhesion and migration, CAMs also serve to directly regulate the response to growth and differentiation factors. This review focuses on the role of CAMs and their signal transduction pathways, where known, in several developmentally regulated processes in the nervous system such as the induction of neural tissue, neuroblast migration, axon growth and guidance, and myelination.

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Increase of ganglioside content on sera of tumor-bearing patients has been observed in many types of cancer and determinations of serum ganglioside profiles have shown that the altered ganglioside species are always the major ones present in the corresponding tumors. Upon surgical treatment of the tumors, the serum ganglioside content returns to normal values, thus suggesting that increased gangliosides in the blood derive from proliferating cancer cells. Shedding involves all cellular ganglosides, but the rate of shedding depends on the ceramide structure, and it is much higher for molecular species containig C16-C20 fatty acids (i.e. the lower band of ganglioside doublets seen by thin-layer chromatography). The mechanism of ganglioside shedding leading to the alteration of the serum profile is not fully understood, but it is very likely that gangliosides are shed as monomeric molecules. Indeed, when micellar gangliosides are injected i.v. to rats, the serum protein distribution at equilibrium show a higher affinity of high density lipoproteins and significant binding to albumin, whereas tumor-shed gangliosides display the same distribution as endogenous gangliosides with the highest proportion on low density lipoproteins and none on alubmin. In vivo, shed gangliosides that are taken up by erythrocytes and leukocytes have an immuno-modulatory effect. Low concentrations might be immunogenic and higher amounts lead to an inhibition of the immune response, although the extent of inhibition gangliosdides depends on the structure of both oligosaccharide and ceramide moieties. The most potent effect concerns the production of interleukin-1 by macrophages and the activity of released interleukin-1 on thymocytes.

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Sulfated fucans and a fucosylated chondroitin sulfate are the major sulfated polysaccharides described in tissues of echinoderms. The connective tissue of the sea cucumber contams high amounts of a fucosylated chondroitin sulfate. This polysaccharide has a chondroitin sulfate-like structure, containing large numbers of sulfated α-L-fucopyranose branches linked to position 3 of the β-D-glucuronic acid residues. Methylation analysis and NMR spectroscopy revealed that the position of the glycosidic linkage and the site of sulfation in the fucose branches are heterogeneous. We proposed a preponderance of disaccharide units formed by 3, 4-di-O-sulfo-α-L-fucopyranosyl units glycosidically linked through position l→2to 4-O-sulfo-α-L-fucopyranose. These unusual fucose branches in the sea cucumber glycosaminoglycan obstruct the access of chondroitinases and hyaluronidases to the chondroitin sulfate core. We speculate that the fucose branches may prevent digestion of the sea cucumber body wall by microorganisms present in the marine environment.
The sulfated fucans from echinoderms have a tetrasaccharide repeat unit in which the separate residues are 1→3-linked α-L-fucopyranose but with difference in the extent and positions of their sulfate substitution. The sea urchin fucan has the structure:
[3-α-L-Fucp-2(OSO₃)-1→3-α-L-Fucp-4(OSO₃)-1→3-α-L-Fucp-2, 4(OSO₃)-1→3-α-L-Fucp-2(OSO₃)-1]n
and the sea cucumber has the structure:
[3-α-L-Fucp-2, 4(OSO₃)1→3-α-L-Fucp-1→3-α-L-Fucp-2(OSO₃)-1→3-α-L-Fucp-2(OSO₃)-1]n
This type of regular structure has not previously been described, and is in contrast with the random arrangement of substituents on the similar 1→3-linkedα-L-fucopyranose backbone of the sulfated fucans from brown algae.
The sulfated polysaccharides described in echinoderms share characteristics with the animal glycosaminoglycans and with the marine algae sulfated polysaccharides. This observation raises interesting questions concerning the evolutionary aspects of these macromolecules. In addition, the sulfated polysaccharides from echinoderms may be important to design new approach to the biological activities or to industrial applications of biopolymers.

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