Neuroligins

Introduction to Neuroligins

Neuroligin is a type of postsynaptic membrane protein that plays an important role in regulating the production of synapses between neurons. Neuroligin can bind to its ligand, β-neurexins, to mediate heterophilic adhesion. Many evidence highlights the importance of these two proteins interacts with each other to enhance dendrite cell adhesion. Moreover, neuroligins can influence the activities of neural networks by altering synaptic function, which regulates signal transmission by recruiting a wide variety of presynaptic and postsynaptic molecules. Pilot studies have also demonstrated that neuroligins are involved in the location of neurotransmitter receptors and channels in the process of cell maturation. Till now, five subtypes of neuroligins, neuroligin 1, 2, 3, 4X, or 4Y, have been identified and have become key factors for neuronal development and the formation of presynaptic terminals.

Neuroligins in Synaptic Development

In recent years, neuroligins have emerged as significant trans-synaptic cell adhesion molecules and have shown promising data in mediating synapse formation, synapse maturation, as well as synapse maintenance. In general, the structure of neuroligins consists of a cholinesterase-like domain, an O-glycosylation domain, a single transmembrane region, as well as a short C-terminal cytoplasmic tail. The overexpression of neuroligins is necessary for both excitatory and inhibitory synapse development. For instance, neuroligin 1 is essential for creating excitatory synapses, and neuroligin 2 is important for inhibitory synapses. Neurexin/neuroligin complex is coated to the junction by PDZ-interacting containing motif and actin filaments. The PDZ-interacting motif can interact with PSD-95 and S-SCAM to further bind with β-catenin and AMPA receptors for synaptic vesicle transmission.

Neuroligins and Autism

The autism spectrum disorder (ASD) is a complex genetic mutation-associated disease and has been broadly studied over the last decade. Current studies have suggested that the dysfunction of neuronal communication caused by different synaptic signaling pathways has been regarded as the underlying risk of ASD. Meanwhile, a range of cell-adhesion proteins that are associated with trans-synaptic signalings, such as neurexins and neuroligins, have become attractive targets for ASD treatment. In a recent study, several NGS analyses have revealed that more than 25 variations or deletions of neurexin and neuroligin genes have been found in patients with a battery of neurodevelopmental disorders, including ASD. Neuroligins are therefore critical for neural synaptic formation, synaptic function, and neural transmission. Besides, a wide spectrum of knockout animal models targeting specific neurexin and neuroligin genes have been established for developing therapies for patients suffering from these genetic diseases.

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