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PMID:17868325

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Citation

Berninghausen, O, Rahman, MA, Silva, JP, Davletov, B, Hopkins, C and Ushkaryov, YA (2007) Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses. J. Neurochem. 103:1855-63

Abstract

Synaptogenesis requires formation of trans-synaptic complexes between neuronal cell-adhesion receptors. Heterophilic receptor pairs, such as neurexin Ibeta and neuroligin, can mediate distinct intracellular signals and form different cytoplasmic scaffolds in the pre- and post-synaptic neuron, and may be particularly important for synaptogenesis. However, the functions of neurexin and neuroligin depend on their distribution in the synapse. Neuroligin has been experimentally assigned to the post-synaptic membrane, while the localization of neurexin remains unclear. To study the subcellular distribution of neurexin Ibeta and neuroligin in mature cerebrocortical synapses, we have developed a novel method for the physical separation of junctional membranes and their direct analysis by western blotting. Using urea and dithiothreitol, we disrupted trans-synaptic protein links, without dissolving the lipid phase, and fractionated the pre- and post-synaptic membranes. The purity of these fractions was validated by electron microscopy and western blotting using multiple synaptic markers. A quantitative analysis has confirmed that neuroligin is localized strictly in the post-synaptic membrane. We have also demonstrated that neurexin Ibeta is largely (96%) pre-synaptic. Thus, neurexin Ibeta and neuroligin normally form trans-synaptic complexes and can transduce bidirectional signals.

Links

PubMed PMC2517655 Online version:10.1111/j.1471-4159.2007.04918.x

Keywords

Animals; Cell Adhesion Molecules, Neuronal; Cell Membrane/metabolism; Cerebral Cortex/cytology; Membrane Proteins/metabolism; Microscopy, Electron, Transmission/methods; Nerve Tissue Proteins/metabolism; Rats; Rats, Sprague-Dawley; Subcellular Fractions/metabolism; Synapses/metabolism; Synapses/ultrastructure; Synaptic Vesicles/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:NRX1B

GO:0042734: presynaptic membrane

ECO:0000314:

C

See Fig 5. Neurexin is largely presynaptic and binds with neuroligin normally to form trans-synaptic complexes and transduce bidirectional signals across the membrane.

complete


See also

References

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