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Publication : Glutamate receptor δ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes.

First Author  Yasumura M Year  2012
Journal  J Neurochem Volume  121
Issue  5 Pages  705-16
PubMed ID  22191730 Mgi Jnum  J:184953
Mgi Id  MGI:5426772 Doi  10.1111/j.1471-4159.2011.07631.x
Citation  Yasumura M, et al. (2012) Glutamate receptor delta1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes. J Neurochem 121(5):705-16
abstractText  Glutamate receptor (GluR) delta1 is widely expressed in the developing forebrain, whereas GluRdelta2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRdelta2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitatory synapse formation in the cerebellum. Thus, a question arises whether GluRdelta1 regulates synapse formation in the forebrain. In this study, we showed that the N-terminal domain of GluRdelta1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRdelta1 expressed in HEK293T cells induced preferentially inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity of GluRdelta1 was suppressed by the addition of the extracellular domain of NRXN1alpha or NRXN1beta containing splice segment 4. Cbln subtypes directly bound to the N-terminal domain of GluRdelta1. The synaptogenic activity of GluRdelta1 in the presence of Cbln subtypes correlated well with their binding affinities. When transfected to cortical neurons, GluRdelta1 stimulated inhibitory synapse formation in the presence of Cbln1 or Cbln2. These results together with differential interactions of Cbln subtypes with NRXN variants suggest that GluRdelta1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with NRXNs containing splice segment 4 through Cbln subtypes.
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