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Nöral hücre adezyon molekülü (Neural cell adhesion molecule, NCAM) veya CD56; iskelet kası, glia, sinir hücrelerinin ve doğal öldürücü hücrelerin yüzeyinde dışa vurulan bir homofilik bağlantı glikoproteinidir. NCAM'ın ya da CD56'nın hücre-hücre yapışmasında, nörit gelişiminde, sinaptik plastisitede, öğrenmede ve bellekte görevinin bulunduğu gösterilmiştir.
Biçimler, etki alanları ve homofilik bağlantı
NCAM immünglobulin(Ig) üst ailesinden(süper ailesinden) bir glikoproteindir. En azından 27 seçenek olarak eklenmiş NCAM mRNA'ları, NCAM izoformlarının geniş bir çeşitliliğini vererek üretilmektedir. CD56'nın üç ana izoformu yalnız kendi sitoplazmik etki alanlarında değişime uğrar:
- NCAM-120 kDa (Glikozil fosfatidil inozitol (GPI) çapalı)
- NCAM-140 kDa (kısa sitoplazmik etki alanı)
- NCAM-180 kDa (uzun sitoplazmik etki alanı)
NCAM'ın hücre dışı etki alanı iki fibronektin tip III (FNIII) etki alanının ardı sıra beş immünglobülin benzeri etki alanını kapsamaktadır. Nörit gelişimine yol açan sinyallenmeyi kapsayan FNIII etki alanları ve NCAM'a homofilik bağlanmayı kapsayan Ig etki alanlarıyla birlikte NCAM'ın farklı etki alanlarının, çeşitli rolleri üstlendiği gösterilmiştir.
Homofilik bağlanma, karşı yüzeylerdeki (trans-) NCAM bileşikleri ile aynı yüzeydeki (cis-) NCAM bileşikleri arasında oluşur. 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. 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.
Posttranslasyonel modifikasyon
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).
Normal hücrelerde dışa vurumu
The neural cell adhesion molecule NCAM1 appears on early and is important in the formation of and their boundaries at sites of .
Later in development, NCAM1 (CD56) expression is found on various differentiated tissues and is a major CAM mediating adhesion among neurons and between neurons and muscle.
İşlev
NCAM is thought to signal to induce neurite outgrowth via the Fibroblast growth factor receptor (FGFR) and act upon the p59Fyn signaling pathway.
In nerves, NCMA1 regulates homophilic (like-like) interactions between neurons and between neurons and muscle; it associates with () and stimulates activity of receptor to induce outgrowth. When cells stop making and , and start displaying , cells separate and migrate.
During , CD56 is the prototypic marker of , also present on subset of and .
In , CD56 contributes to or during .
Patoloji
- Anatomik patolojide patologlar, CD56'yı immünhistokimya ile kimi tümörlerin tanısında kullanmaktadır.
- CD56 ile olumlu boyanan normal hücreler; doğal ölüdürücü (NK) hücreleri, etkinleşmiş T hücrelerini, bunun yanı sıra beyin, beyincik ve nöroendokrin dokuları kapsamaktadır.
- CD56 olumlu olan tümörler; multipl miyelom, miyeloid lösemi, nöroendokrin tümörleri, Wilms tümörü, nöroblastom, NK/T hücre lenfoması, pankreatik asiner hücreli karsinom, feokromositom, paragangliyoma, küçük hücreli akciğer karsinomu ve Ewing sarkomu tümör ailesi olarak söylenebilir.
Alzheimers
NCAM2 is found in lower levels in synapses in the hippocampuses of Alzheimers sufferers and is found to be broken down by beta-amyloid
Anti-NCAM tedavisi
NCAM deneysel olarak antikor tabanlı immün tedavide bir hedef bileşiği gibi kullanılmaktadır. 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.
Kaynakça
- ^ . 20 Şubat 2018 tarihinde kaynağından arşivlendi. Erişim tarihi: 18 Ocak 2016.
- ^ Reyes AA, Small SJ, Akeson R. (1991).
- ^ a b Suzuki M, Angata K, Nakayama J, Fukuda M. (2003).
- ^ Becker, C. G., Artola, A., Gerardy-Schahn, R., Becker, T., Welzl, H., and Schachner, M. (1996).
- ^ Stoenica L, Senkov O, Gerardy-Schahn R, Weinhold B, Schachner M, Dityatev A. (2006).
- ^ Senkov O, Sun M, Weinhold B, Gerardy-Schahn R, Schachner M, Dityatev A. (2006).
- ^ Leshchyns'ka I, Liew HT, Shepherd C, Halliday GM, Stevens CH, Ke YD, Ittner LM, Sytnyk V (2015). "Aβ-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer's disease". Nature Communications. Cilt 6. s. 8836. doi:10.1038/ncomms9836. (PMID) 26611261.
- ^ Jensen M, Berthold F. (2007).
Dış bağlantılar
- Neural Cell Adhesion Molecule at the US National Library of Medicine Medical Subject Headings (MeSH)
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Noral hucre adezyon molekulu Neural cell adhesion molecule NCAM veya CD56 iskelet kasi glia sinir hucrelerinin ve dogal oldurucu hucrelerin yuzeyinde disa vurulan bir homofilik baglanti glikoproteinidir NCAM in ya da CD56 nin hucre hucre yapismasinda norit gelisiminde sinaptik plastisitede ogrenmede ve bellekte gorevinin bulundugu gosterilmistir Bicimler etki alanlari ve homofilik baglantiNCAM immunglobulin Ig ust ailesinden super ailesinden bir glikoproteindir En azindan 27 secenek olarak eklenmis NCAM mRNA lari NCAM izoformlarinin genis bir cesitliligini vererek uretilmektedir CD56 nin uc ana izoformu yalniz kendi sitoplazmik etki alanlarinda degisime ugrar NCAM 120 kDa Glikozil fosfatidil inozitol GPI capali NCAM 140 kDa kisa sitoplazmik etki alani NCAM 180 kDa uzun sitoplazmik etki alani NCAM in hucre disi etki alani iki fibronektin tip III FNIII etki alaninin ardi sira bes immunglobulin benzeri etki alanini kapsamaktadir Norit gelisimine yol acan sinyallenmeyi kapsayan FNIII etki alanlari ve NCAM a homofilik baglanmayi kapsayan Ig etki alanlariyla birlikte NCAM in farkli etki alanlarinin cesitli rolleri ustlendigi gosterilmistir Homofilik baglanma karsi yuzeylerdeki trans NCAM bilesikleri ile ayni yuzeydeki cis NCAM bilesikleri arasinda olusur 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 exonsAnother 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 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 Posttranslasyonel modifikasyonNCAM 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 Normal hucrelerde disa vurumuThe neural cell adhesion molecule NCAM1 appears on early and is important in the formation of and their boundaries at sites of Later in development NCAM1 CD56 expression is found on various differentiated tissues and is a major CAM mediating adhesion among neurons and between neurons and muscle IslevNCAM is thought to signal to induce neurite outgrowth via the Fibroblast growth factor receptor FGFR and act upon the p59Fyn signaling pathway In nerves NCMA1 regulates homophilic like like interactions between neurons and between neurons and muscle it associates with and stimulates activity of receptor to induce outgrowth When cells stop making and and start displaying cells separate and migrate During CD56 is the prototypic marker of also present on subset of and In CD56 contributes to or during PatolojiAnatomik patolojide patologlar CD56 yi immunhistokimya ile kimi tumorlerin tanisinda kullanmaktadir CD56 ile olumlu boyanan normal hucreler dogal oludurucu NK hucreleri etkinlesmis T hucrelerini bunun yani sira beyin beyincik ve noroendokrin dokulari kapsamaktadir CD56 olumlu olan tumorler multipl miyelom miyeloid losemi noroendokrin tumorleri Wilms tumoru noroblastom NK T hucre lenfomasi pankreatik asiner hucreli karsinom feokromositom paragangliyoma kucuk hucreli akciger karsinomu ve Ewing sarkomu tumor ailesi olarak soylenebilir AlzheimersNCAM2 is found in lower levels in synapses in the hippocampuses of Alzheimers sufferers and is found to be broken down by beta amyloidAnti NCAM tedavisiNCAM deneysel olarak antikor tabanli immun tedavide bir hedef bilesigi gibi kullanilmaktadir 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 Kaynakca 20 Subat 2018 tarihinde kaynagindan arsivlendi Erisim tarihi 18 Ocak 2016 Reyes AA Small SJ Akeson R 1991 a b Suzuki M Angata K Nakayama J Fukuda M 2003 Becker C G Artola A Gerardy Schahn R Becker T Welzl H and Schachner M 1996 Stoenica L Senkov O Gerardy Schahn R Weinhold B Schachner M Dityatev A 2006 Senkov O Sun M Weinhold B Gerardy Schahn R Schachner M Dityatev A 2006 Leshchyns ka I Liew HT Shepherd C Halliday GM Stevens CH Ke YD Ittner LM Sytnyk V 2015 Ab dependent reduction of NCAM2 mediated synaptic adhesion contributes to synapse loss in Alzheimer s disease Nature Communications Cilt 6 s 8836 doi 10 1038 ncomms9836 PMID 26611261 Jensen M Berthold F 2007 Dis baglantilarNeural Cell Adhesion Moleculeat the US National Library of Medicine Medical Subject Headings MeSH