Mucin-Type O-Glycosylation in Invertebrates

Abstract

Abstract:O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood. However, the regulation of the processes and the molecular aspects of defects, especially in correlation with cancer or developmental abnormalities, are still under investigation. The knowledge of the correlating invertebrate systems and evolutionary aspects of these highly conserved biosynthetic events may help improve the understanding of the regulatory factors of this pathway. Invertebrates display a broad spectrum of glycosylation varieties, providing an enormous potential for glycan modifications which may be used for the design of new pharmaceutically active substances. Here, overviews of the present knowledge of invertebrate mucin-type O-glycan structures and the currently identified enzymes responsible for the biosynthesis of these oligosaccharides are presented, and the few data dealing with functional aspects of O-glycans are summarised.

Lectin PLL3, a Novel Monomeric Member of the Seven-Bladed β-Propeller Lectin Family

“…Nevertheless, the natural binding partner of PLL3 can be a fucosylated oligosaccharide of insect or nematode origin that was not present in the tested set. Fucosylated oligosaccharides were identified in both insects [25,26] and nematodes [27]; however, the glycobiology of these organisms is not well investigated yet.…”

Early ovariectomy reveals the germline encoding of natural anti‐A‐ and Tn‐cross‐reactive immunoglobulin M (IgM) arising from developmental O‐GalNAc glycosylations. (Germline‐encoded natural anti‐A/Tn cross‐reactive IgM)

“…Tn‐ and T‐ glycosylation is not restricted to higher metazoan organisms. These O ‐glycosylations are already used by mollusks , and the T antigen appears to be normally expressed on the surface of eggs and liver cells of Schistosoma mansoni . Sera from patients infected with this worm produce antibodies against cancerous tissue, whereas experimentally infected mice generate antibodies against Tn and T antigenic epitopes .…”

“…The egg‐protecting hemagglutinating protein from H. pomatia has been established as a tumor cell marker and a prognostic indicator of different human tumor cell lineages , and its hexameric structure may give rise to speculation regarding an evolutionary relationship to the mammalian nonimmune or ancestral immunoglobulin M. These molluscan agglutinins are produced in the albumen gland (connected to the oviduct), and emerging from the coat proteins of fertilized eggs. They most likely reflect the snail‐intrinsic, reversible O ‐GalNAc glycosylations , initiating protein glycosylations even in mollusks . While the agglutinins are engaged in self‐defense, the agglutinin‐free hemocyanin from H. pomatia (HPH) exerted strong anti‐proliferative effects in murine models of colon carcinoma .…”

“…The metabolic relationship of the Tn and T antigens to other developmental antigens, such as the heterogenetic Forssman antigen, with the structure GalNAc α 1‐3GalNAc β 1‐3Gal α 1‐4Gal β 1‐4Glc‐R, remains unknown. While Tn and T are common trans‐species, metazoan structures that occur even in mollusks , one must differentiate between Forssman‐positive (F+) metazoans, such as mice, and the Forrsman negative (F‐) human. Hakomori et al described chemically and immunologically detectable levels of the Forssman glycolipid as a normal component of the human gastrointestinal mucosa , while they discovered Forssman glycolipids in the tumors of F‐ individuals but did not find them in F+ individuals.…”

“…Not spontaneously occurring in plant species [13], the Tn antigen is a common metazoan eukaryotic structure, which arises from O ‐GalNAc glycosylations, used already by mollusks and insects, like the fruit fly Drosophila melanogaster but when arrested in nondevelopmental tissues of higher metazoans, such as mammals, signifies malignancy, while the degree of HPA binding correlates with the stages of various kinds of metastatic cancer, irrespectively of the organ . Furthermore, when animal tumors are associated with Tn antigen expression , it is important to mention that the HPA binding sites are identical to that in human tumors and appear to change similarly with tumor stage.…”