Extracellular Proteins Binding Glutamate Receptors

A new concept is the bridging of receptors and ion channels across the extracellular space in the central nervous system (CNS) (reviewed in ref. 87), which was first discovered at the neuromuscular junction. For example, PSD-95 can form a link between NMDA receptors and neuroligin. Neuroligin is a protein with a single transmembrane domain that is expressed at the postsynaptic membrane and can associate in the extracellular space with neurexin. Neurexin binds to the PDZ domain of CASK, which, via its SH3 domain, binds to calcium channels located in the presynaptic membrane. Neuroli-gin can induce presynaptic differentiation in neurons. Another secreted surface molecule that clusters GluR1-3 is Narp (neuronal activity-regulated pentraxin). Narp was cloned as an immediate early gene with a long half-life induced by seizures (88). Narp is expressed presynaptically and postsynaptically at excitatory synapses in the hippocampus and the spinal cord and induces GluR1 aggregation (89).

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