Glycoprotein
Japanese












Biosynthesis of Oligo/Polysialic Acid

 The oligo/polysialic acid (oligo/polySia) glycotope represents a group of oligo/polymers of Sia consisting of N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and deaminoneuraminc acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) (Fig. 1). The linkages between sialic acid residues are known to be alpha2->5O glycolyl, alpha2->8, alpha2->9, and alpha2->8/9. As shown in Table 1, many examples of the presence of oligo/polySia-containing glycoproteins have been demonstrated in eukaryotes, including recent findings of frequent occurrence of oligoSia structure on glycoproteins in mammals(1). Oligo/polySia structures on glycoproteins are widely recognized as regulator for cell-cell communication during development and cell differentiation based on various features such as stage- and tissue-specific expression, a large diversity in their structures, and unique physicochemical properties as polyanions (2). Biosynthesis of oligo/polySia is presumed to be complicated because of the large spectrum of their structures, which arises from the degree of polymerization (DP=2-100), variations in the (-ketosidic linkages to the penultimate Sia residues (alpha2->5O glycolyl, alpha2->8, and alpha2->9), and the composition of monomeric Sia (Neu5Ac, Neu5Gc, and KDN), which are often modified by O-acetylation, O-lactylation, O-sulfation, and lactonization). Here the biosynthesis of oligo/polySia chains of glycoproteins are described. Those for polySia (DP=100-200), which occurs on neuroinvasive bacterial capsular polysaccharide, and oligoSia (DP=2-4), which are often found in glycolipids, are not included.
Figure
(a) Oligo/polysialic acid on O-linked glycoproteins
The oligo/polySia chains on polysialoglycoproteins (PSGP) of rainbow trout have been demonstrated to be synthesized as follows (3).
Figure
The oligo/polySia chains are synthesized by three enzymes, (2,6-sialyltransferase (alpha2,6ST), alpha2,8-sialyltransferase (alpha2,8ST, initiase), and alpha2,8-polysialyltranseferase (alpha2,8polyST, polymerase) in Golgi apparatus and/or cortical vesicles. The elongation of the chains is found to be terminated by introducing one KDN residue to the non-reducing terminal sialic acid residue in the alpha2->8-linkage. Enzymes involved in O-acetylation and O-lactylation of the Sia residues in PSGP have not yet been identified.
The biosynthesis of alpha2->8-linked oligoKDN found in KDN-gp of rainbow trout ovarian fluid (4) and alpha2->5O glycolyl-linked oligo/polyNeu5Gc found in polySia-gp of sea urchin jelly coat (5) has not yet been studied. Interestingly, in the latter case, 9-O-sulfation of non-reducing terminal Neu5Gc residue is suggested to play a role as the termination signal.


(b) Oligo/polysialic acid on N-linked glycoproteins
The elucidation of biosynthesis of polySia on neural cell adhesion molecule (N-CAM) has made big advances by the identification and cloning of two alpha2,8-sialyltransferases (Table II), from mouse (6), Chinese hamster (7), and human (8). The present understanding of the pathways for oligo/polysialylation on N-linked glycan chains is summarized as follows.
Figure
The alpha2,8-polysialyltransferase(s) (alpha2,8polyST) which catalyzes elongation reaction is considered to be ST8Sia II (STX) and/or ST8Sia IV (PST). However, it still remains to be clarified if the alpha2,8ST which initiates formation of oligo/polySia is a different enzyme from alpha2,8polySTs. Recently, not only expression of the enzymes ST8Sia II and ST8Sia IV, but also intracellular Ca2+ has been shown to control the biosynthesis of polySia on N-CAM (9). Structural analysis of carbohydrate chains derived from embryonic N-CAM indicates that O-acetylation of polySia may be related to the termination of elongation (10).
The biosynthetic pathway for oligoSia chains on glycoproteins other than N-CAM is unknown; however, ST8Sia III (Table 2) catalyzing formation of dimer of alpha2->8linked Sia on N-linked glycoproteins may possibly be involved.


Elucidation of mechanisms for biosynthesis of other types of oligo/polySia chains, such as alpha2->5O glycolyl linked oligo/polyNeu5Gc and alpha2->9 linked oligo/polySia, modifications of sialic acid residues, and termination of elongation of oligo/polySia chains is interesting future work on biosynthesis of oligo/polySia.
Chihiro Sato (Nagoya University)
Ken Kitajima (Nagoya University Bioscience Center)
References (1) C. Sato, H. Fukuoka, K. Ohta, T. Matsuda, R. Koshino, K. Kobayashi, F. A. Troy II, and K. Kitajima: Frequent occurrence of pre-existing alpha2,8-linked disialic and oligosialic acids with chain lengths up to 7 Sia residues in mammalian brain glycoproteins. J. Biol. Chem. 275, 15422-15431, 2000
(2) Troy, FA II : Polysialylation:from bacteria to brains. Glycobiology 2, 5-23, 1992
(3) Kitazume, S, Kitajima, K, Inoue, S, Inoue, Y, Frederic, A, Troy, FA II : Developmental expression of trout egg polysialoglycoproteins and the prerequisite a2,6-, and a2,8-sialyl and a2,8-polysialyltransferase activities required for their synthesis during oogenesis. J. Biol. Chem. 269, 10330-10340, 1994
(4) Kanamori, A, Inoue, S, Iwasaki, M, Kitajima, K, Kawai, G, Yokoyama, S, Inoue, Y : Deaminated neuraminic acid-rich glycoprotein of rainbow trout egg vitelline envelope. J. Biol. Chem. 265, 21811-21819, 1990
(5) Kitazume, S, Kitajima, K, Inoue, S, Troy, FA II, Cho, J-W, Lennarz, W J, Inoue, Y : Identification of polysialic acid-containing glycoprotein in the jelly coat of sea urchin eggs. J. Biol. Chem. 269, 22712-22718, 1994
(6) Tsuji, S : Molecular cloning and functional analysis of sialyltransferases. J. Biochem. 120, 1-13, 1996
(7) Eckhart, M, Muhlenhoff, M, Betth, A, Koopman, J, Frosch, M, Gerardy-Schahn, R : Molecular cloning of eukaryotic polysialyltransferase I. Nature 373, 715-718, 1995
(8) Nakayama, J, Fukuda, MN, Fredette, B, Ranscht, B, Fukuda, M : Expression cloning of a human polysialyltransferase that forms the polysialylated neural cell adhesion molecule present in embryonic brain. Proc. Natl. Acad. Sci. U.S.A. 92, 7031-7035, 1995
(9) Bruses, J L,Rutishauser, U : Regulation of neural cell adhesion molecule polysialylation . J.Cell. Biol. 140, 1177-1186, 1998
(10) Kudo, M, Kitajima, K, Inoue, S, Shiokawa, K, Morris, HR, Dell, A, Inoue : Characterization of the major core structures of the a28-linked polysialic acid-containing glycan chains present in neural cell adhesion molecule in embryonic chick brain. J. Biol. Chem. 271, 32667-32677, 1996
Apr. 15, 2001

GlycoscienceNow INDEXReturn to Top Page