Abstract
Although it has been over 20 years since Neural Cell Adhesion Molecule 2 (NCAM2) was identified as the second member of the NCAM family with a high expression in the nervous system, the knowledge of NCAM2 is still eclipsed by NCAM1. The first studies with NCAM2 focused on the olfactory bulb, where this protein has a key role in axonal projection and axonal/dendritic compartmentalization. In contrast to NCAM1, NCAM2’s functions and partners in the brain during development and adulthood have remained largely unknown until not long ago. Recent studies have revealed the importance of NCAM2 in nervous system development. NCAM2 governs neuronal morphogenesis and axodendritic architecture, and controls important neuron-specific processes such as neuronal differentiation, synaptogenesis and memory formation. In the adult brain, NCAM2 is highly expressed in dendritic spines, and it regulates synaptic plasticity and learning processes. NCAM2’s functions are related to its ability to adapt to the external inputs of the cell and to modify the cytoskeleton accordingly. Different studies show that NCAM2 interacts with proteins involved in cytoskeleton stability and proteins that regulate calcium influx, which could also modify the cytoskeleton. In this review, we examine the evidence that points to NCAM2 as a crucial cytoskeleton regulation protein during brain development and adulthood. This key function of NCAM2 may offer promising new therapeutic approaches for the treatment of neurodevelopmental diseases and neurodegenerative disorders.
Highlights
Neurons express a large variety of membrane proteins involved in multiple processes.These proteins act as a link between the extracellular environment and the intracellular compartment, and mediate different processes
With all the data and observations presented in this review, we can hypothesize that Neural Cell Adhesion Molecule 2 (NCAM2) contributes to the neuronal molecular identity and is crucial for the neuronal functions—see Figure 4
In the development of the nervous system, NCAM2 regulates the molecular recognition that allows the formation of contacts between axonal and dendritic compartments leading to the formation of synapses and neural circuits
Summary
Neurons express a large variety of membrane proteins involved in multiple processes. These proteins act as a link between the extracellular environment and the intracellular compartment, and mediate different processes. Several studies and hypotheses relate particular combinations of CAMs to a specific molecular identity of each neuron This identity can be crucial for the processes that take place during brain development and adult maintenance, such as axon guidance, membrane recognition and neuronal network formation [6,7,8,9,10,11]. There are various genomic studies that link adhesion proteins with mental retardation and psychiatric disorders, such as autism and schizophrenia [15,16,17] These pathologies show altered neuronal development and connectivity [18]. Reduced levels in plasma from adolescents with early-onset psycosis
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