Polypeptide variation in an N-CAM extracellular immunoglobulin-like fold is developmentally regulated through alternative splicing

Small, Stephen; Haines, Susan L.; Akeson, Richard

doi:10.1016/0896-6273(88)90158-4

Cited by 112 publications

(62 citation statements)

References 51 publications

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“…We also demonstrate that exon a is expressed in 6.7, 5.2 and 2.9 kb mRNAs, but not in the 7.4 kb mRNA. Finally, we confirm the findings of [8] that all NCAM mRNA size classes consist of two forms: one containing the Pi-exon and another lacking this exon. …”

Section: Introductionsupporting

confidence: 90%

“…There are five different NCAM mRNA size classes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb in adult rat brain [6]. More than 20 different exons are described that code for the distinct NCAM polypeptides [5,[7][8][9][10][11]. In the genome several small exons exist…”

Section: Introductionmentioning

confidence: 99%

“…Another exon, SEC, that presumably generates a secreted form of NCAM and is demonstrated in human muscle and mouse brain [13] may also be inserted between exon 12 and 13. An exon, called Pi, consisting of 30 bp, can be inserted between exon 7 and 8 [8] (see Fig. I).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

et al. 1990

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Neural cell adhesion molecule; Northern blotting; Oligonucleotide A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized the five NCAM mRNAs in rat brain.

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Section: Introductionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

et al. 1990

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“…It was recently demonstrated that PSA expression in ciliary ganglion neurons of chick embryo was regulated by PSA synthase level (23). However, it has been shown that the alterations in the extracellular polypeptide structure of NCAM caused by alternative splicing affected the polysialylation of NCAM (31)(32)(33). Therefore, the structural change of NCAM due to a variable alternative spliced exon and the structural changes of N-glycans also regulates the PSA expression level (30,33).…”

Section: St8sia II (Stx) Is An Ncam-specific Psa Synthasementioning

confidence: 99%

Characterization of Mouse ST8Sia II (STX) as a Neural Cell Adhesion Molecule-specific Polysialic Acid Synthase

Kojima

Tachida

Yoshida

et al. 1996

Journal of Biological Chemistry

116

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Polysialic acid (PSA) 1 is an unusual carbohydrate associated with the neural cell adhesion molecule (NCAM) and the ␣-subunit of the voltage-gated sodium channel in mammals and is more abundant in embryonic than adult brain (1-3). PSA is implicated in the reduction of NCAM adhesion through its large negative charge and thereby allows increased neurite outgrowth and cell motility (4 -6). It is also reported that the presence of PSA affects cell-cell interactions through other adhesion molecules (7). Although functions of PSA have been described, little is known about the mechanisms by which the synthesis and expression of PSA are regulated.PSA on NCAM has so far been considered to be synthesized through the actions of at least two distinct enzymes, i.e. an initiator ␣2,8-sialyltransferase, which adds a single ␣2,8-linked sialic acid to ␣2,3-linked sialic acid residues on N-glycans, and a polysialyltransferase, which adds multiple ␣2,8-linked sialic acid residues (8). Livingston and Paulson (9) cloned STX/ST8Sia II, a new member of the sialyltransferase gene family from rat. Recently, we showed that ST8Sia II/STX cloned from mouse can synthesize PSA on ␣2,3-sialylated Nglycans of glycoproteins without an initiator ␣2,8-sialyltransferase in vitro and direct in vivo synthesis of PSA in several cells (10,11). In addition, we cloned mouse ST8Sia IV by homology cloning using the sequence information on GD3 synthase (12) and STX (9) and showed that the mouse enzyme can synthesize PSA, like ST8Sia II/STX (13). Eckhardt et al. (14) also cloned a sialyltransferase, which is involved in the biosynthesis of PSA on NCAM from hamster, namely PST-1. Hamster PST-1 showed 99.2% identity to mouse ST8Sia IV, indicating that the hamster enzyme is a counterpart of mouse ST8Sia IV. The gene expression of mouse ST8Sia II was restricted in the brain and was dramatically up-and down-regulated during developmental stages of the brain like the expression of PSA, whereas mouse ST8Sia IV was strongly expressed in lung and heart rather than brain, and only little regulation was observed during brain development (10, 13). These observations suggest that ST8Sia II/STX rather than ST8Sia IV/PST-1 is involved in the biosynthesis of PSA associated with NCAM during mouse brain development. However, there is no evidence that the PSA on NCAM is specifically synthesized by ST8Sia II in vivo as well as in vitro, because PSA was synthesized on some glycoproteins such as fetuin in vitro (11), and the transfection of the human STX gene into NCAM-negative cells also caused the expression of PSA on the cell surface (15).The present study focuses on the biosynthesis of PSA by mouse ST8Sia II using a recombinant soluble NCAM fused with the Fc region of human IgG1 (NCAM-Fc) and comparison of the activities of mouse ST8Sia II and IV. ST8Sia II specifically and directly synthesized PSA on ␣2,3-linked sialic acid residues of N-glycans of specific isoforms of NCAM, without

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“…However, the alternate splicing of the extracellular IIa domain, in combination with two possible intracellular forms, one of which may be phosphorylated (1), suggests that alteration in these molecular structures could play an important role in recognition and signal transduction. Similar observations gave been made for other Ig-like molecules, most notably the fibroblast growth factor receptor (15,25,29).Defining the size and diversity of the BGP family is a first step in exploring a functional role. Toward this end, we surveyed the RNAs of many different normal tissues and transformed cell lines by polymerase chain reaction (PCR) amplification of the specific extracellular and intracellular regions of BGP mRNAs that are known to be alternatively spliced and code for one of several isoforms.…”

mentioning

confidence: 62%

Human biliary glycoprotein gene: characterization of a family of novel alternatively spliced RNAs and their expressed proteins.

Barnett¹,

Drake²,

Pickle³

1993

Mol. Cell. Biol.

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80% [5]) while retaining the characteristic Ig-like folds. The overall Ig-like character imparted to BGP molecules suggests that they function as receptors, perhaps involved in adhesion (23, 37). However, the alternate splicing of the extracellular IIa domain, in combination with two possible intracellular forms, one of which may be phosphorylated (1), suggests that alteration in these molecular structures could play an important role in recognition and signal transduction. Similar observations gave been made for other Ig-like molecules, most notably the fibroblast growth factor receptor (15,25,29).Defining the size and diversity of the BGP family is a first step in exploring a functional role. Toward this end, we surveyed the RNAs of many different normal tissues and transformed cell lines by polymerase chain reaction (PCR) amplification of the specific extracellular and intracellular regions of BGP mRNAs that are known to be alternatively spliced and code for one of several isoforms. By this process, we found additional size classes of amplified products that differ substantially from those previously described. Further characterization of these segments revealed that they code for two novel non-Ig-like extracellular domains derived by alternative splicing fromAlu-like elements, as well as another form that codes for a BGP isoantigen with only an N terminus anchored via a TM domain to a cytoplasmic tail. Some of these forms appear to be represented more in RNAs from tumor-derived cells than in RNAs from normal tissue counterparts, suggesting that the transformed phenotype may contribute to the appearance of new BGP splice variants and their translated polypeptides.The finding of additional novel forms of BGP extends the

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Polypeptide variation in an N-CAM extracellular immunoglobulin-like fold is developmentally regulated through alternative splicing

Cited by 112 publications

References 51 publications

Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

Characterization of Mouse ST8Sia II (STX) as a Neural Cell Adhesion Molecule-specific Polysialic Acid Synthase

Human biliary glycoprotein gene: characterization of a family of novel alternatively spliced RNAs and their expressed proteins.

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