Nöral hücre adezyon molekülü

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 embryonic cells and is important in the formation of cell collectives and their boundaries at sites of morphogenesis.
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 fibroblast growth factor receptor (FGFR) and stimulates tyrosine kinase activity of receptor to induce neurite outgrowth. When neural crest cells stop making N-CAM and N-cadherin, and start displaying integrin receptors, cells separate and migrate.
During hematopoiesis, CD56 is the prototypic marker of NK cells, also present on subset of CD4+ T cells and CD8+ T cells.
In cell adhesion, CD56 contributes to cell-cell adhesion or cell-matrix adhesion during embryonic development.
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.