The Neural Cell Adhesion Molecule (NCAM) as a Regulator of Cell-Cell Interactions

Rutishauser, Urs; Acheson, Ann; Hall, Alison K.; Mann, Dennis M.; Sunshine, Jeffrey L.

doi:10.1126/science.3281256

Cited by 756 publications

(371 citation statements)

References 38 publications

Supporting

Mentioning

354

Contrasting

Unclassified

Order By: Relevance

Section: Resultsmentioning

confidence: 99%

“…Based on an average estimation of 54 ng immobilized [12], such aggregate formation is not encouraged. In any case, the simplest explanation of adhesion in doublets is consistent with the reports of Rutishauser et al [12], who show that greater than 80°70 of NCAM molecules in their preparations exist as monomers or dimers. Fab' fragments of polyclonal anti-NCAM antibodies were able to interfere with NCAM homophilic binding by up to 5007o compared to OFab' fragments (Fab' fragments prepared from preimmune serum) further verifying the specificity of the NCAM-NCAM interaction (table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Abbreviations: P0 NCAM, neural cell adhesion molecule isolated from newborn rat brains; P40 NCAM, NCAM isolated from rat brains at postnatal day 40; PBS, phosphate-buffered saline; PSA, polysialic acid NCAM-mediated adhesion appears to occur by a homophilic and possibly polyvalent binding mechanism [1, 11,12] in which NCAM on the surface of one cell binds to NCAM on an opposing cell. Studies by Cole and Glaser [10] have demonstrated that cell surface NCAM also participates in cell-substratum interactions in the developing chick nervous system.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of the kinetics of neural cell adhesion molecule homophilic binding

Moran

Bock

1988

FEBS Letters

View full text Add to dashboard Cite

A solid-phase assay has been developed for the investigation of the kinetics of neural cell adhesion molecule (NCAM) binding. Using this assay we can show that NCAM binds to itself in a time-dependent and saturable manner. Binding constants (KB values) of 6.9 x 10 -s M and 1.23 x 10 -~ M, respectively, were obtained for adult and newborn rat NCAM homophilic binding. Binding is specifically inhibited by Fab' fragments of polyclonal anti-NCAM antibodies but is unaffected by heparin or ehondroitin sulphate. This indicates that the NCAM homophilic binding site is separate from and independent of the heparin-binding site and that a developmental modification, probably polysialation, gives rise to marked differences in the adhesive properties of NCAM.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of the kinetics of neural cell adhesion molecule homophilic binding

Moran

Bock

1988

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…It is interesting to note that mouse NK cells do not express CD56 whereas reciprocally human NK cells do not express CD146. CD146 and CD56 share many characteristics: the former is sialylated and the latter is polysialylated in the extracellular domain [29,30], there is no consensus about the ligands, the genes are located on the same chromosome (9 in mice and 11 in human) and their expression defines two NK cell subsets. The function of CD56 on human NK cells is unknown.…”

Section: Discussionmentioning

confidence: 99%

Mouse CD146/MCAM is a marker of natural killer cell maturation

et al. 2008

View full text Add to dashboard Cite

CD146/melanoma cell adhesion molecule is an adhesion molecule expressed by endothelial cells and by a small fraction of activated T and B lymphocytes in humans. In order to analyze the pattern of CD146 expression in mouse leukocytes at steady-state conditions, we generated a set of novel rat anti-mouse CD146 monoclonal antibodies. CD146 expression was undetectable on monocytes, dendritic cells, T cells or B cells, but was expressed on about 30% of neutrophils and 60% of NK cells. Within murine lymphocytes, CD146 was defined as a novel NK-specific surface molecule. An increased percentage of CD146 1 cells was found in the most mature CD27 À CD11b 1 NK cell subpopulation, which also displays higher expression of Ly49C/I, Ly49D and KLRG1 and lower expression of NKG2A/C/E molecules. CD146 1 NK cells were found to be less cytotoxic and produce less IFN-c than CD146 À NK cells upon stimulation with target cells or activating antibodies. These findings define CD146 as a marker of mouse NK cell maturation that may be used as an alternative to the combined use of CD27 and CD11b staining to detect final stages of NK cell maturation.Key words: Adhesion . Antibodies . CD146/MCAM . Maturation . NK cells Introduction CD146, also known as melanoma cell adhesion molecule (MCAM or Mel-CAM), MUC18, S-Endo1, A32 antigen, is an integral membrane glycoprotein of 113 kDa that belongs to the Ig superfamily with a characteristic V-V-C2-C2-C2 domain structure [1]. Two others members of this family have been identified in humans: basal-cell adhesion molecule and activated leukocytecell adhesion molecule, also called CD166 [2,3]. Basal-cell adhesion molecule is a splice variant of the Lutheran blood group glycoprotein that is reported to bind laminin [3]. Activated leukocyte-cell adhesion molecule is a costimulatory molecule mediating homophilic interaction and heterophilic interaction with CD6 and is involved in activation and trafficking of leukocytes into the central nervous system [4]. CD146 was originally defined as a marker of tumor progression and metastasis formation in human melanoma [5]. Overexpression of CD146 in CD146-negative melanoma cells renders these cells highly metastatic after injection in immunodeficient mice [6]. Moreover, injection of a humanized anti-CD146 mAb in immunodeficient mice bearing human melanomas significantly reduces the tumor size and the number of metastases [7]. The adhesive functions of CD146 were demonstrated using a solid-phase adhesion test in which both CD146-positive and CD146-negative melanoma cells bound to eucaryotic recombinant CD146 protein, suggesting that CD146 can mediate both homophilic and heterophilic interaction with an as yet unidentified ligand [8,9]. Using S-Endo1 mAb, we previously detected cell surface expression of CD146 on human vascular endothelial cells, whatever vessel caliber or anatomical region [10]. On cultured endothelial cells, CD146 is mainly located at the intercellular junctions and is involved in inter-endothelial cell adhesion and paracellular permeability [11,1...

show abstract

“…Attachment of sialic acid polymers through α-2,8 binding to NCAM leads to formation of a polysialylated form of the molecule, namely polysialic acid-NCAM (PSA-NCAM) with modified adhesive properties [6]. PSA-NCAM is expressed in pancreatic beta cells of adult rats and has been used to sort rat beta cells [7].…”

Section: Introductionmentioning

confidence: 99%

A simple two-step protocol for the purification of human pancreatic beta cells

Banerjee

Otonkoski

2009

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Isolated pure human beta cells would be helpful for a number of research purposes. However, lack of beta cell-specific surface antigens has been a major problem. We aimed to develop a simple method for human beta cell isolation based on the initial elimination of ductal cells by their expression of carbohydrate antigen 19-9 (CA19-9), followed by positive selection of beta cells by their expression of polysialic acid-neural cell adhesion molecule (PSA-NCAM). Methods Cell type-specific expression of CA19-9, NCAM and PSA-NCAM was studied in sections of adult human pancreas and in cultured primary endocrine and exocrine cells. Dispersed human islet cells were purified in two steps, after 4 days of suspension culture, by binding to magnetic microbeads coupled to antibodies against CA19-9 and PSA-NCAM. Results NCAM expression was detected in ducts and islets in the human pancreas. In contrast, PSA-NCAM immunoreactivity was detected only in islets. PSA-NCAM staining in dispersed cells revealed that the marker is expressed in all endocrine cell types, but not in duct cells. Purification of dispersed islet cells using PSA-NCAM microbeads alone did not completely eliminate contaminating duct cells. However, elimination of the duct cells by CA19-9 microbeads followed by positive sorting of the PSA-NCAM-positive cells in five consecutive islet preparations resulted in 90 to 98% pure endocrine cells, of which 89 to 97% were beta cells. Conclusions/interpretation We describe a simple and reproducible method for purification of viable human pancreatic beta cells devoid of exocrine acini and ducts.

show abstract

The Neural Cell Adhesion Molecule (NCAM) as a Regulator of Cell-Cell Interactions

Cited by 756 publications

References 38 publications

Characterization of the kinetics of neural cell adhesion molecule homophilic binding

Characterization of the kinetics of neural cell adhesion molecule homophilic binding

Mouse CD146/MCAM is a marker of natural killer cell maturation

A simple two-step protocol for the purification of human pancreatic beta cells

Contact Info

Product

Resources

About