Neuroligin 1 is a Postsynaptic Cell-adhesion Molecule of Excitatory Synapses

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Feb 3

PMID 9927700

Citations 313

Authors

J Y Song

K Ichtchenko

T C Sudhof

N Brose

Affiliations

Soon will be listed here.

Abstract

At the synapse, presynaptic membranes specialized for vesicular traffic are linked to postsynaptic membranes specialized for signal transduction. The mechanisms that connect pre- and postsynaptic membranes into synaptic junctions are unknown. Neuroligins and beta-neurexins are neuronal cell-surface proteins that bind to each other and form asymmetric intercellular junctions. To test whether the neuroligin/beta-neurexin junction is related to synapses, we generated and characterized monoclonal antibodies to neuroligin 1. With these antibodies, we show that neuroligin 1 is synaptic. The neuronal localization, subcellular distribution, and developmental expression of neuroligin 1 are similar to those of the postsynaptic marker proteins PSD-95 and NMDA-R1 receptor. Quantitative immunogold electron microscopy demonstrated that neuroligin 1 is clustered in synaptic clefts and postsynaptic densities. Double immunofluorescence labeling revealed that neuroligin 1 colocalizes with glutamatergic but not gamma-aminobutyric acid (GABA)ergic synapses. Thus neuroligin 1 is a synaptic cell-adhesion molecule that is enriched in postsynaptic densities where it may recruit receptors, channels, and signal-transduction molecules to synaptic sites of cell adhesion. In addition, the neuroligin/beta-neurexin junction may be involved in the specification of excitatory synapses.

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References

Ushkaryov Y, Petrenko A, Geppert M, Sudhof T . Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science. 1992; 257(5066):50-6. DOI: 10.1126/science.1621094. View

Navone F, Jahn R, Di Gioia G, Stukenbrok H, Greengard P, De Camilli P . Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol. 1986; 103(6 Pt 1):2511-27. PMC: 2114586. DOI: 10.1083/jcb.103.6.2511. View

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Rickmann M, Wolff J . S100 protein expression in subpopulations of neurons of rat brain. Neuroscience. 1995; 67(4):977-91. DOI: 10.1016/0306-4522(94)00615-c. View

Ullrich B, Ushkaryov Y, Sudhof T . Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron. 1995; 14(3):497-507. DOI: 10.1016/0896-6273(95)90306-2. View

Ichtchenko K, Hata Y, Nguyen T, Ullrich B, Missler M, Moomaw C . Neuroligin 1: a splice site-specific ligand for beta-neurexins. Cell. 1995; 81(3):435-43. DOI: 10.1016/0092-8674(95)90396-8. View

Brose N, Huntley G, Sharma G, Morrison J, Heinemann S . Differential assembly of coexpressed glutamate receptor subunits in neurons of rat cerebral cortex. J Biol Chem. 1994; 269(24):16780-4. View

Siegel S, Brose N, Janssen W, Gasic G, Jahn R, Heinemann S . Regional, cellular, and ultrastructural distribution of N-methyl-D-aspartate receptor subunit 1 in monkey hippocampus. Proc Natl Acad Sci U S A. 1994; 91(2):564-8. PMC: 42989. DOI: 10.1073/pnas.91.2.564. View

10.

Goodman C, Shatz C . Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell. 1993; 72 Suppl:77-98. DOI: 10.1016/s0092-8674(05)80030-3. View

11.

Ichtchenko K, Nguyen T, Sudhof T . Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem. 1996; 271(5):2676-82. DOI: 10.1074/jbc.271.5.2676. View

12.

Hunt C, Schenker L, Kennedy M . PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses. J Neurosci. 1996; 16(4):1380-8. PMC: 6578559. View

13.

Goodman C . Mechanisms and molecules that control growth cone guidance. Annu Rev Neurosci. 1996; 19:341-77. DOI: 10.1146/annurev.ne.19.030196.002013. View

14.

Uchida N, Honjo Y, Johnson K, Wheelock M, Takeichi M . The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol. 1996; 135(3):767-79. PMC: 2121068. DOI: 10.1083/jcb.135.3.767. View

15.

Song J, van Marle J, Van Noorden C, Frederiks W . Redistribution of Ca2+, Mg2+-ATPase activity in relation to alterations of the cytoskeleton and tight junctions in hepatocytes of cholestatic rat liver. Eur J Cell Biol. 1996; 71(3):277-85. View

16.

Chiba A, Keshishian H . Neuronal pathfinding and recognition: roles of cell adhesion molecules. Dev Biol. 1996; 180(2):424-32. DOI: 10.1006/dbio.1996.0316. View

17.

Song J, van Marle J, Van Noorden C, Frederiks W . Disturbed structural interactions between microfilaments and tight junctions in rat hepatocytes during extrahepatic cholestasis induced by common bile duct ligation. Histochem Cell Biol. 1996; 106(6):573-80. DOI: 10.1007/BF02473272. View

18.

Daly C, Ziff E . Post-transcriptional regulation of synaptic vesicle protein expression and the developmental control of synaptic vesicle formation. J Neurosci. 1997; 17(7):2365-75. PMC: 6573495. View

19.

Inoue A, Sanes J . Lamina-specific connectivity in the brain: regulation by N-cadherin, neurotrophins, and glycoconjugates. Science. 1997; 276(5317):1428-31. DOI: 10.1126/science.276.5317.1428. View

20.

Kornau H, Seeburg P, Kennedy M . Interaction of ion channels and receptors with PDZ domain proteins. Curr Opin Neurobiol. 1997; 7(3):368-73. DOI: 10.1016/s0959-4388(97)80064-5. View