Discover

(Redirected from CD56)

'Neural Cell Adhesion Molecule' (NCAM, also the cluster of differentiation 'CD56') is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. NCAM has been implicated as having a role in cell-cell adhesion,^[1] neurite outgrowth, synaptic plasticity, and learning and memory.

Contents

Forms, domains and homophilic binding

Minor exons

Posttranslational modification

Function

Pathology

References

External links

Forms, domains and homophilic binding

There are at least 27 alternatively spliced NCAM mRNAs produced giving a wide diversity of NCAM isoforms ^[2]. The three main isoforms of NCAM vary only in their cytoplasmic domain:

★ NCAM-120kDa (GPI anchored)

★ NCAM-140kDa (short cytoplasmic domain)

★ NCAM-180kDa (long cytoplasmic domain)
The extracellular domain of NCAM consists of five immunoglobulin-like (Ig) domains followed by two fibronectin type III (FNIII) domains. The different domains of NCAM have been shown to have different roles with the Ig domains being involved in homophilic binding to NCAM, and the FNIII domains being involved signalling leading to neurite outgrowth.
Homophilic binding occurs between NCAM molecules on opposing surfaces (''trans-'') and NCAM molecules on the same surface (''cis-'')1. There is much controversy as to how exactly NCAM homophilic binding is arranged both in trans- and ''cis-''. Current models suggest ''trans-'' homophilic binding occurs between two NCAM molecules binding antiparallel between all five Ig domains or just IgI and IgII. ''cis-'' homophilic binding is thought to occur by interactions between both IgI and IgII, and IgI and IgIII, forming a higher order NCAM multimer. Both ''cis-'' and ''trans-'' NCAM homophilic binding have been shown to be important in NCAM “activation” leading to neurite outgrowth.

Minor exons

Another layer of complexity is created by the insertion of other "minor" exons in the NCAM transcript. The two most notable are:

★ the VASE ('VA'riable domain 'S'pliced 'E'xon) exon which is thought to correlate with an inbition of the neurite outgrowth promoting properties of NCAM.

★ the MSD ('M'uscle 'S'pecific 'D'omain), which is thought to play a positive role in myoblast fusion ^[3]. In skeletal muscle it is found in all three NCAM isoforms, increasing their MW, giving NCAM-125, NCAM-145, and NCAM-185 isoforms, but is most commonly found in the NCAM-125 isoform ^[3].

Posttranslational modification

NCAM can be posttranslationally modified by the addition of polysialic acid (PSA) to the fifth Ig domain which is thought to abrogate its homophilic binding properties and can lead to reduced cell adhesion important in cell migration and invasion. PSA has been shown to be critical in learning and memory. Removal of PSA from NCAM by the enzyme endoneuraminidase (EndoN) has been shown to abolish long term potentiation (LTP) and long term depression (LDP)^[5][6][7].

Function

NCAM is thought to signal to induce neurite outgrowth via the Fibroblast growth factor receptor (FGFR) and act upon the p59Fyn signalling pathway.

Pathology

In anatomic pathology, pathologists make use of CD56 immunohistochemistry to recognize certain tumors.

★ Normal cells that stain positively for CD56 include NK cells, activated T cells, the brain and cerebellum, and neuroendocrine tissues.

★ Tumors that are CD56-positive are myeloma, myeloid leukemia, neuroendocrine tumors, Wilms' tumor, adult neuroblastoma, NK/T cell lymphomas, pancreatic acinar cell carcinoma, pheochromocytoma, and small cell lung carcinoma. (Ewing's sarcoma / PNET is CD56 negative.)

References

1. Pathology Outlines
2. At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA are expressed during rat heart development., Reyes AA, Small SJ, Akeson R., , , Mol Cell Biol., 1991
3. Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion., Suzuki M, Angata K, Nakayama J, Fukuda M., , , J Biol Chem., 2003
4. Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion., Suzuki M, Angata K, Nakayama J, Fukuda M., , , J Biol Chem., 2003
5. The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation., Becker, C. G., Artola, A., Gerardy-Schahn, R., Becker, T., Welzl, H., and Schachner, M., , , J Neurosci Res., 1996
6. In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid., Stoenica L, Senkov O, Gerardy-Schahn R, Weinhold B, Schachner M, Dityatev A., , , Eur J Neurosci., 2006
7. Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation and memory acquisition and consolidation in a fear-conditioning paradigm., Senkov O, Sun M, Weinhold B, Gerardy-Schahn R, Schachner M, Dityatev A., , , J Neurosci., 2006

External links

★