Neuroligin

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Dimer of two mouse neuroligin-1 cholinesterase-like domains (magenta and cyan) in complex with two neurexin-beta1 LNS6 domains (salmon and yellow) and Ca+2 ions (green) 3b3q

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Function

Neuroligins (NLGN) are a family of postsynaptic proteins which bind to the presynaptic Neurexin (NRXN) to form a complex which attaches neurons. In humans the NLGN family contains 4 to 5 members that are numbered 1, 2, 3, 4X and 5 or 4Y^[1].

See Neurodevelopmental Disorders

Neuroligin-Neurexin Interaction

NLGN-1 regulates spines and synaptic plasticity^[2].
NLGN-2 is localized to inhibitory synapses^[3].
NLGN-3 is a synapse organizer which shapes normal function and autism disorder^[4].
NLGN-4 is localized to glyceric post-synapses and regulates retina inhibition^[5].

Disease

Mutations in NLGN 4 are associated with autism and mental retardation^[6].

Structural insights

The NLGN-NRXN complex involves the octahedrally coordinated Ca+2 ion^[7]. Water molecules are shown as red spheres.

↑ Fabrichny IP, Leone P, Sulzenbacher G, Comoletti D, Miller MT, Taylor P, Bourne Y, Marchot P. Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion. Neuron. 2007 Dec 20;56(6):979-91. PMID:18093521 doi:10.1016/j.neuron.2007.11.013
↑ Liu A, Zhou Z, Dang R, Zhu Y, Qi J, He G, Leung C, Pak D, Jia Z, Xie W. Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. J Cell Biol. 2016 Feb 15;212(4):449-63. doi: 10.1083/jcb.201509023. PMID:26880202 doi:https://dx.doi.org/10.1083/jcb.201509023
↑ Varoqueaux F, Jamain S, Brose N. Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol. 2004 Sep;83(9):449-56. PMID:15540461 doi:https://dx.doi.org/10.1078/0171-9335-00410
↑ Budreck EC, Scheiffele P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur J Neurosci. 2007 Oct;26(7):1738-48. doi: 10.1111/j.1460-9568.2007.05842.x. PMID:17897391 doi:https://dx.doi.org/10.1111/j.1460-9568.2007.05842.x
↑ Hoon M, Soykan T, Falkenburger B, Hammer M, Patrizi A, Schmidt KF, Sassoe-Pognetto M, Lowel S, Moser T, Taschenberger H, Brose N, Varoqueaux F. Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3053-8. doi:, 10.1073/pnas.1006946108. Epub 2011 Jan 31. PMID:21282647 doi:https://dx.doi.org/10.1073/pnas.1006946108
↑ Zhang C, Milunsky JM, Newton S, Ko J, Zhao G, Maher TA, Tager-Flusberg H, Bolliger MF, Carter AS, Boucard AA, Powell CM, Sudhof TC. A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. J Neurosci. 2009 Sep 2;29(35):10843-54. doi: 10.1523/JNEUROSCI.1248-09.2009. PMID:19726642 doi:https://dx.doi.org/10.1523/JNEUROSCI.1248-09.2009
↑ Chen X, Liu H, Shim AH, Focia PJ, He X. Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16. PMID:18084303 doi:10.1038/nsmb1350

3D Structures of Neuroligin

24-March-2026

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, David Canner, Pascale Marchot, Jaime Prilusky, Joel L. Sussman

[1] Fabrichny IP, Leone P, Sulzenbacher G, Comoletti D, Miller MT, Taylor P, Bourne Y, Marchot P. Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion. Neuron. 2007 Dec 20;56(6):979-91. PMID:18093521 doi:10.1016/j.neuron.2007.11.013

[2] Liu A, Zhou Z, Dang R, Zhu Y, Qi J, He G, Leung C, Pak D, Jia Z, Xie W. Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. J Cell Biol. 2016 Feb 15;212(4):449-63. doi: 10.1083/jcb.201509023. PMID:26880202 doi:https://dx.doi.org/10.1083/jcb.201509023

[3] Varoqueaux F, Jamain S, Brose N. Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol. 2004 Sep;83(9):449-56. PMID:15540461 doi:https://dx.doi.org/10.1078/0171-9335-00410

[4] Budreck EC, Scheiffele P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur J Neurosci. 2007 Oct;26(7):1738-48. doi: 10.1111/j.1460-9568.2007.05842.x. PMID:17897391 doi:https://dx.doi.org/10.1111/j.1460-9568.2007.05842.x

[5] Hoon M, Soykan T, Falkenburger B, Hammer M, Patrizi A, Schmidt KF, Sassoe-Pognetto M, Lowel S, Moser T, Taschenberger H, Brose N, Varoqueaux F. Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3053-8. doi:, 10.1073/pnas.1006946108. Epub 2011 Jan 31. PMID:21282647 doi:https://dx.doi.org/10.1073/pnas.1006946108

[6] Zhang C, Milunsky JM, Newton S, Ko J, Zhao G, Maher TA, Tager-Flusberg H, Bolliger MF, Carter AS, Boucard AA, Powell CM, Sudhof TC. A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. J Neurosci. 2009 Sep 2;29(35):10843-54. doi: 10.1523/JNEUROSCI.1248-09.2009. PMID:19726642 doi:https://dx.doi.org/10.1523/JNEUROSCI.1248-09.2009

[7] Chen X, Liu H, Shim AH, Focia PJ, He X. Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16. PMID:18084303 doi:10.1038/nsmb1350

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Neuroligin

Function

Disease

Structural insights

3D Structures of Neuroligin

References

Proteopedia Page Contributors and Editors (what is this?)

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