神経細胞接着分子

関: NCAM、neural cell adhesion molecule

WordNet

small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
a fibrous band of scar tissue that binds together normally separate anatomical structures
abnormal union of bodily tissues; most common in the abdomen
(physics and chemistry) the simplest structural unit of an element or compound

PrepTutorEJDIC

(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
粘着,付着
分子《略》『mol』) / (一般に)(…の)微量《+『of』+『名』》
神経単位,神経細胞,ニューロン,ノイロン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/06/12 16:29:44」(JST)

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

Forms, domains and homophilic binding

NCAM is a glycoprotein of Immunoglobulin(Ig)superfamily. At least 27 alternatively spliced NCAM mRNAs are 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 signaling 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 (VAriable domain Spliced Exon) exon which is thought to correlate with an inhibition of the neurite outgrowth promoting properties of NCAM.
the MSD (Muscle Specific Domain), 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 exhibits glycoforms as it 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 (LTD).^[4]^[5]^[6]

Function

NCAM is thought to signal to induce neurite outgrowth via the Fibroblast growth factor receptor (FGFR) and act upon the p59Fyn signaling 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, paraganglioma, small cell lung carcinoma, and the Ewing's Sarcoma Family of Tumors.

Anti-NCAM therapy

NCAM has been used as a target molecule for experimental antibody-based immunotherapy. Successful radioimmunolocalisation of metastases was demonstrated after giving injections of NCAM-binding 123J-UJ13a or 131J-UJ13a radioimmunoconjugates to children with neuroblastoma. Patients with small cell lung cancer were treated with the anti-NCAM immunotoxine huN901-DM1 in two different clinical studies, revealing acceptable toxicity and signs of clinical response.^[7]

References

^ Pathology Outlines
^ Reyes AA, Small SJ, Akeson R. (1991). "At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA are expressed during rat heart development". Mol Cell Biol. 11 (3): 1654–61. PMC 369464. PMID 1996115. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=369464.
^ ^a ^b Suzuki M, Angata K, Nakayama J, Fukuda M. (2003). "Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion". J Biol Chem. 278 (49): 49459–68. DOI:10.1074/jbc.M308316200. PMID 13679364.
^ Becker, C. G., Artola, A., Gerardy-Schahn, R., Becker, T., Welzl, H., and Schachner, M. (1996). "The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation". J Neurosci Res. 45 (2): 143–52. DOI:10.1002/(SICI)1097-4547(19960715)45:2<143::AID-JNR6>3.0.CO;2-A. PMID 8843031.
^ Stoenica L, Senkov O, Gerardy-Schahn R, Weinhold B, Schachner M, Dityatev A. (2006). "In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid". Eur J Neurosci. 23 (9): 2255–64. DOI:10.1111/j.1460-9568.2006.04771.x. PMID 16706834.
^ Senkov O, Sun M, Weinhold B, Gerardy-Schahn R, Schachner M, Dityatev A. (2006). "Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation and memory acquisition and consolidation in a fear-conditioning paradigm". J Neurosci. 26 (42): 10888–109898. DOI:10.1523/JNEUROSCI.0878-06.2006. PMID 17050727.
^ Jensen M, Berthold F. (2007). "Targeting the neural cell adhesion molecule in cancer". Cancer Lett. 258 (1): 9–21. DOI:10.1016/j.canlet.2007.09.004. PMID 17949897.

External links

Neural+Cell+Adhesion+Molecule at the US National Library of Medicine Medical Subject Headings (MeSH)

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リンク元	「NCAM」「神経細胞接着分子」
関連記事	「adhesion」「neuronal」「neuronal cell」「molecule」「cell」

「NCAM」

Neural cell adhesion molecule 1
	; PDB rendering based on 1epf.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2E3V, 2HAZ, 2VKW, 2VKX, 3MTR
Identifiers
Symbols	NCAM1; CD56; MSK39; NCAM
External IDs	OMIM: 116930 MGI: 97281 HomoloGene: 40754 GeneCards: NCAM1 Gene
EC number	2.7.11.1
Gene Ontology
Molecular function	• protein binding; • GPI anchor binding;
Cellular component	• Golgi membrane; • extracellular region; • plasma membrane; • external side of plasma membrane; • cell surface; • integral to membrane; • axon; • anchored to membrane; • neuronal cell body;
Biological process	• cell adhesion; • axon guidance; • cytokine-mediated signaling pathway; • homotypic cell-cell adhesion; • positive regulation of calcium-mediated signaling; • interferon-gamma-mediated signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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