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Neuroligin (NLGN), a type I membrane protein, is a protein on the postsynaptic membrane that mediates synapse formation between neurons. Neuroligins mediate signaling across the synapse and affect the properties of neural networks by specifying synaptic functions. In humans, alterations in genes encoding neuroligins are implicated in autism and other cognitive diseases.[2] It has been shown that neuroligin expression induces contact-mediated presynaptic differentiation in contacting axons.[3]

The extracellular domain of NLGN consists mostly of a region that is homologous to acetylcholinesterases, but the amino acids important for catalysis in AChE are not conserved in NLGN, which lack esterase activity. Furthermore, this AChE homologous region is crucial for the proper function of NLGN.[3]

Neuroligins act as ligands for β-Neurexins, which are located presynaptically. Neuroligin and β-neurexin "shake hands," resulting in the connection between the two neurons and the production of a synapse.[3] Additionally, neuroligin has also been found to play a role in angiogenesis.[4]

Neuroligins also operate in honeybees and their functional roles in insects are likely similar to those in vertebrates.[5]

Known neuroligin genes include NLGN1, NLGN2, NLGN3, NLGN4X, and NLGN5.


  1. Fabrichny IP, et al. (2007). Structural Analysis of the Synaptic Protein Neuroligin and Its β-Neurexin Complex: Determinants for Folding and Cell Adhesion. Neuron 56 (6): 979–91.
  2. Südhof TC (October 2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455 (7215): 903–11.
  3. 3.0 3.1 3.2 Scheiffele P, Fan J, Choih J, Fetter R, Serafini T (June 2000). Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101 (6): 657–69.
  4. Bottos A, Destro E, Rissone A, et al. (November 2009). The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions. Proceedings of the National Academy of Sciences of the United States of America 106 (49): 20782.
  5. Biswas S, Russell RJ, Jackson CJ, et al. (2008). Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera. PloS ONE 3 (10): e3542.

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