A role for sorting nexin 27 in AMPA receptor trafficking
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 w...
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Main Authors: | , , , , |
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Format: | Article |
Language: | English |
Published: |
2014
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Subjects: | |
Online Access: | https://hdl.handle.net/10356/80929 http://hdl.handle.net/10220/19359 |
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Institution: | Nanyang Technological University |
Language: | English |
Summary: | 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 Ca2þ/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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