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Publication : A role for sorting nexin 27 in AMPA receptor trafficking.

First Author  Loo LS Year  2014
Journal  Nat Commun Volume  5
Pages  3176 PubMed ID  24458027
Mgi Jnum  J:346408 Mgi Id  MGI:6213490
Doi  10.1038/ncomms4176 Citation  Loo LS, et al. (2014) A role for sorting nexin 27 in AMPA receptor trafficking. Nat Commun 5:3176
abstractText  Sorting nexin 27 (SNX27), a PDZ domain-containing endosomal protein, was recently shown to modulate glutamate receptor recycling in Down's syndrome. However, the precise molecular role of SNX27 in GluA1 trafficking is unclear. Here we report that SNX27 is enriched in dendrites and spines, along with recycling endosomes. Significantly, the mobilization of SNX27 along with recycling endosomes into spines was observed. Mechanistically, SNX27 interacts with K-ras GTPase via the RA domain; and following chemical LTP stimuli, K-ras is recruited to SNX27-enriched endosomes through a Ca(2+)/CaM-dependent mechanism, which in turn drives the synaptic delivery of homomeric GluA1 receptors. Impairment of SNX27 prevents LTP and associated trafficking of AMPARs. These results demonstrate a role for SNX27 in neuronal plasticity, provide a molecular explanation for the K-ras signal during LTP and identify SNX27 as the PDZ-containing molecular linker that couples the plasticity stimuli to the delivery of postsynaptic cargo.
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