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The neural cell adhesion molecule, or NCAM for short, is a molecule of the immunoglobulin family found in eukaryotes that mediates interactions among different types of neural cells throughout the body, often in conjunction with neurotransmitters.

Function

Neural cell adhesion molecule (NCAM) is a gene located on chromosome 11 that codes for a glycoprotein contained in the immunoglobulin family. NCAM aids in cell-to-cell interactions and cell-matrix interactions (NCBI, 2018). It functions through homophilic interactions and has been implicated in cell binding, migration, and differentiation (DeLellis et al., 2011).

The homophilic (antigen-specific) binding mechanisms of NCAM, which affect cell-to-cell interaction, are regulated by differential expression of polysialic acid (PSA) carbohydrates (DeLellis et al., 2011), which interfere with cell-to-cell adhesion by reducing intercellular contact forces. NCAM-PSA is formed when long homopolymers of sialic residues are attached to NCAM during posttranslational modification. (Fiszbein et al., 2015).

NCAM can facilitate the movement of across neural membranes in order to increase the amount of intracellular calcium in neurons.

Disease

Mutations in NCAM proteins can also cause many different disorders of the gastrointestinal system. These can range from inherited diseases, such as Hirschsprung's disease, to noninherited diseases such as fetal alcohol syndrome and chronic intestinal obstruction in newborns. These diseases arise due to mutations in NCAM genes that prevent the protein from allowing pacemaker cells in the gut, called interstitial cells of Cajal, to communicate. For diseases affecting newborns, such as chronic intestinal obstruction, the symptoms can disappear with age if these interstitial cells of Cajal develop properly. For people with other diseases or for those that do not develop these cells with age, treatments such as enema are employed.

NCAM mutations have also been linked to the growth of tumor cells, and often are found in advanced-stage tumors. These mutations allow NCAM to facilitate the adhesion of tumor cells and allow the tumor to grow very large very rapidly. The mutations also allow the cancer cells to more easily move through the body, invade healthy tissues, and form tumors there, as the mutated NCAM allows the cancer cells to bind to other autocrine/paracrine cells. The most effective treatment for cancers with NCAM mutations is full removal of the tumor, but this is most effective in very early stage tumors. Currently, different drugs that serve as NCAM immunotoxins are in trials to kill the mutated NCAM in more advanced tumors.

Relevance

The presence of NCAM is required to mediate interactions between many different neural cells throughout the body. NCAM also plays a huge role in facilitating interactions between fetal cells during embryogenesis. It has many different possible forms, as well as many different sites that perform many different tasks related to cell interactions. Without the presence of NCAM, fetuses could not develop properly, and the nervous systems in the living organisms would not be able to function properly, as the neural cells would not be able to communicate. The many different tasks that NCAM performs are vital for the survival of an organism.

Structural highlights

NCAM consists of one distinct polypeptide chain, two copies of which combine to form a homodimer. Each polypeptide is 191 amino acids long and contains four chains: the A, B, C, and D chains.

The extracellular region of NCAM includes five immunoglobulin and two fibronectin type III domains (Fiszbein, 2015).

The FN1 region is particularly important for enabling polysialylation of Ig5, and so the is particularly important for the role of NCAM as a regulator of cell-to-cell interaction.

The s, in particular, have been implicated in polysialylation (Foley et al., 2010), as well as the highlighted acid patch (Thompson et al., 2010).