NCAM - neural cell adhesion molecule | Elisa - Clia - Antibody - Protein

Background

The Neural Cell Adhesion Molecule (NCAM), also known as CD56, is a member of the immunoglobulin superfamily involved in cell-cell adhesion, crucial for the development and maintenance of the nervous system. It was first identified as a glycoprotein on the surface of neural cells and has since been recognized as playing significant roles in cell signaling, synaptic plasticity, and neurodevelopment. NCAM is expressed not only in neurons but also in glial cells, muscle cells, and natural killer cells, reflecting its broad functional importance.

Protein Structure

NCAM exists in several isoforms generated by alternative splicing, the three major forms being NCAM-120, NCAM-140, and NCAM-180, named based on their molecular weights. These isoforms share a common extracellular domain composed of five immunoglobulin-like (Ig-like) domains and two fibronectin type III (FNIII) domains. However, they differ in their intracellular domains:

1. NCAM-120: This isoform is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor, which means it lacks a transmembrane and intracellular domain. This structure facilitates its role in signal transduction and cell adhesion through interactions with other cell surface molecules and the extracellular matrix.
2. NCAM-140: This isoform has a single transmembrane domain and a short cytoplasmic tail. It is primarily involved in cell adhesion and signal transduction processes that influence cellular morphology and motility.
3. NCAM-180: The largest isoform, NCAM-180, also has a transmembrane domain but features a longer cytoplasmic domain, which is essential for its role in synaptic plasticity and long-term potentiation (LTP), key processes in learning and memory.

Classification and Subtypes

NCAM can be classified based on its expression patterns and functional roles:

1. Polysialylated NCAM (PSA-NCAM): This form of NCAM is heavily modified with polysialic acid, which reduces its adhesive properties. PSA-NCAM is predominantly expressed during neural development, facilitating cell migration and plasticity. In adults, it is involved in neurogenesis, synaptic remodeling, and plasticity.
2. Non-Polysialylated NCAM: Found in mature neural tissues, this form mediates strong cell-cell adhesion, maintaining the structure and function of neural circuits.

Function and Biological Significance

NCAM is involved in various critical biological processes:

1. Cell Adhesion: NCAM mediates homophilic and heterophilic cell-cell interactions, essential for the formation and maintenance of neural networks. It interacts with other cell adhesion molecules, extracellular matrix components, and intracellular signaling molecules to regulate adhesion strength and specificity.
2. Neuronal Development: During development, NCAM plays a pivotal role in neurite outgrowth, axon guidance, and synaptogenesis. It helps guide neurons to their appropriate targets, forming functional neural circuits.
3. Synaptic Plasticity: NCAM, particularly NCAM-180, is crucial for synaptic plasticity, influencing synapse formation, stability, and modulation. This function is vital for learning and memory processes.
4. Cell Signaling: Through interactions with intracellular signaling pathways, NCAM influences cellular responses such as migration, differentiation, and survival. It interacts with receptor tyrosine kinases, such as the fibroblast growth factor receptor (FGFR), to modulate downstream signaling pathways.
5. Neuroprotection: NCAM can confer neuroprotective effects under conditions of stress or injury, aiding in the maintenance and repair of neural tissues.

Clinical Issues

Aberrations in NCAM expression and function are implicated in several clinical conditions:

1. Neuropsychiatric Disorders: Altered NCAM expression is associated with schizophrenia, bipolar disorder, and autism. These disorders may result from disruptions in neural connectivity and plasticity linked to NCAM dysfunction.
2. Neurodegenerative Diseases: Reduced levels of PSA-NCAM have been observed in Alzheimer’s disease and other neurodegenerative conditions, correlating with impaired synaptic plasticity and neurogenesis.
3. Cancer: NCAM is expressed in certain tumors, such as neuroblastoma, small cell lung cancer, and multiple myeloma. Its expression is often linked to tumor progression, metastasis, and poor prognosis. NCAM-targeted therapies, such as antibody-drug conjugates and CAR T-cell therapies, are being explored for their potential to treat these malignancies.
4. Muscle Diseases: NCAM expression is upregulated in muscle regeneration and repair processes. Abnormal NCAM expression is noted in muscular dystrophies and inflammatory myopathies.

Summary

NCAM is a multifunctional cell adhesion molecule that plays critical roles in neural development, synaptic plasticity, and cell signaling. It exists in multiple isoforms, each contributing to its diverse functions in various tissues. The clinical significance of NCAM is underscored by its involvement in neuropsychiatric disorders, neurodegenerative diseases, cancer, and muscle diseases. Ongoing research aims to further elucidate the molecular mechanisms underlying NCAM’s functions and develop targeted therapies for conditions associated with NCAM dysfunction. Understanding NCAM's roles in cellular processes is essential for developing new therapeutic strategies for a wide range of diseases.