Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C.

Nybroe, Ole; Albrechtsen, Merete; Dahlin, Jan; Linnemann, Dorte; Lyles, Joan M.; Møller, Claus J.; Bock, Elisabeth

doi:10.1083/jcb.101.6.2310

Cited by 75 publications

(53 citation statements)

References 36 publications

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“…A third polypeptide is seen in small and variable amounts in chicken N-CAM (3, 10) and more consistently in mouse N-CAM (4,30). From its size (Mr, 120,000), the position of the hydrophobic segment in pEC208, and its properties (28,31), it should contain little if any intracellular region and may even lack a membrane-spanning region; we therefore propose the designation ssd (smallest domain) polypeptide.…”

Section: Discussionmentioning

confidence: 99%

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

Hemperly¹,

Murray²,

Edelman³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

146

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Purified fractions of the neural cell-adhesion molecule N-CAM from embryonic chicken brain contain two similar polypeptides (Mr, 160,000 and 130,000), each containing an amino-terminal external binding region, a carbohydrate-rich central region, and a carboxyl-terminal region that is associated with the cell. Previous studies indicate that the two polypeptides arise by alternative splicing of mRNAs transcribed from a single gene. We report here the 3556-nucleotide sequence of a cDNA clone (pEC208) that encodes 964 amino acids from the carbohydrate and cell-associated domains of the larger N-CAM polypeptide followed by 664 nucleotides of 3' untranslated sequence. The predicted protein sequence contains attachment sites for polysialic acid-containing oligosaccharides, four tandem homologous regions of polypeptide resembling those seen in the immunoglobulin superfamily, and a single hydrophobic sequence that appears to be the membrane-spanning segment. The cytoplasmic domain carboxyl terminal to this segment includes a block of approximately equal to 250 amino acids present in the larger but not in the smaller N-CAM polypeptide. We designate these the ld (large domain) polypeptide and the sd (small domain) polypeptide. The intracellular domains of the ld and sd polypeptides are likely to be critical for cell-surface modulation of N-CAM by interacting in a differential fashion with other intrinsic proteins or with the cytoskeleton.

show abstract

Section: Discussionmentioning

confidence: 99%

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

Hemperly¹,

Murray²,

Edelman³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

146

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“…N-CAM (15,16) has an important regulatory role in the developing nervous system and is present in adult nervous tissue. It has been found in astrocytes in vivo (17) and in primary astrocyte cultures (18), although normal levels of N-CAM in glia are low in comparison to those in neurons (19). The amount of N-CAM expressed in the whole nervous system (20,21) and on the surface of astrocytes (22) decreases significantly as the CNS matures compared to the amount seen during prenatal and early postnatal development.…”

mentioning

confidence: 99%

The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes.

Sporns

Edelman

Crossin

1995

Proc. Natl. Acad. Sci. U.S.A.

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Cell proliferation is a key primary process during neural development and also plays an important role in the regenerative response of neural tissue to injury. It has been reported that glial cell proliferation is, at least in part, controlled by a neuronal signal, possibly involving cell surface molecules. We report here that the addition of purified rat neural cell adhesion molecule (N-CAM) to primary cultures of rat forebrain astrocytes inhibits their proliferation. This inhibitory effect can be elicited in cultures grown in chemically defined serum-free medium or in medium that had been supplemented with growth factors. Polyclonal antibodies to N-CAM or their Fab' fragments elicited a similar inhibitory effect. The magnitude of the inhibitory effect of N-CAM was dependent on cell density: it was maximal at low cell densities and weakened progressively as cells approached confluency. Synthetic peptides with sequences identical to a putative homophilic binding region of N-CAM mimicked the effect of purified N.CAM, while peptides of the same length and amino acid composition but with a randomized sequence did not. The addition of N-CAM antisense oligonucleotides to primary astrocyte cultures for 48 h resulted in reduced levels of N-CAM expression. After N-CAM levels on astrocytes were diminished by this treatment, the antiproliferative effect of N-CAM added to the medium was significantly reduced. The combined results suggest that N-CAM homophilic binding may be involved in the control of glial cell proliferation.

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“…Furthermore, the ICD of NCAM contains a palmitoylation site (PS) consisting of four cysteins, and palmitoylation of this site targets NCAM-140 and -180 to lipid rafts [4,15,16]. Whereas NCAM-120 is almost exclusively present in rafts as a consequence of its GPI anchor, NCAM-140 and -180 are found in both raft and nonraft membrane fractions [8,[17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Direct demonstration of NCAMcis-dimerization and inhibitory effect of palmitoylation using the BRET²technique

et al. 2010

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a b s t r a c tBiological activity of the neural cell adhesion molecule (NCAM) depends on both adhesion and activation of intra-cellular signaling. Based on in vitro experiments with truncated extra-cellular domains, several models describing homophilic NCAM trans-and cis-interactions have been proposed. However, cis-dimerization in living cells has not been shown directly and the role of the cytoplasmic part in NCAM dimerization is poorly understood. Here, we used the bioluminescence resonance energy transfer (BRET 2 ) technique to directly demonstrate that full-length NCAM cishomodimerizes in living cells. Based on BRET 2 50 values we suggest that the intra-cellular part of NCAM inhibits cis-dimerization, an effect mainly dependent on the palmitoylation sites.

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Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C.

Cited by 75 publications

References 36 publications

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes.

Direct demonstration of NCAMcis-dimerization and inhibitory effect of palmitoylation using the BRET²technique

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Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C.

Cited by 75 publications

References 36 publications

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes.

Direct demonstration of NCAMcis-dimerization and inhibitory effect of palmitoylation using the BRET2technique

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Direct demonstration of NCAMcis-dimerization and inhibitory effect of palmitoylation using the BRET²technique