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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sg-ntu-dr.10356-809292022-02-16T16:29:36Z A role for sorting nexin 27 in AMPA receptor trafficking Loo, Li Shen Tang, Ning Al-Haddawi, Muthafar Stewart Dawe, Gavin Hong, Wanjin Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Medicine 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version 2014-05-19T01:48:17Z 2019-12-06T14:17:38Z 2014-05-19T01:48:17Z 2019-12-06T14:17:38Z 2014 2014 Journal Article Loo, L. S., Tang, N., Al-Haddawi, M., Stewart Dawe, G., & Hong, W. (2014). A role for sorting nexin 27 in AMPA receptor trafficking. Nature Communications, 5, 3176. 2041-1723 https://hdl.handle.net/10356/80929 http://hdl.handle.net/10220/19359 10.1038/ncomms4176 24458027 en Nature communications © 2014 Macmillan Publishers Limited. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature Communications, Macmillan Publishers Limited. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI:http://dx.doi.org/10.1038/ncomms4176]. application/pdf application/pdf |
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DRNTU::Science::Medicine Loo, Li Shen Tang, Ning Al-Haddawi, Muthafar Stewart Dawe, Gavin Hong, Wanjin A role for sorting nexin 27 in AMPA receptor trafficking |
description |
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. |
author2 |
Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Loo, Li Shen Tang, Ning Al-Haddawi, Muthafar Stewart Dawe, Gavin Hong, Wanjin |
format |
Article |
author |
Loo, Li Shen Tang, Ning Al-Haddawi, Muthafar Stewart Dawe, Gavin Hong, Wanjin |
author_sort |
Loo, Li Shen |
title |
A role for sorting nexin 27 in AMPA receptor trafficking |
title_short |
A role for sorting nexin 27 in AMPA receptor trafficking |
title_full |
A role for sorting nexin 27 in AMPA receptor trafficking |
title_fullStr |
A role for sorting nexin 27 in AMPA receptor trafficking |
title_full_unstemmed |
A role for sorting nexin 27 in AMPA receptor trafficking |
title_sort |
role for sorting nexin 27 in ampa receptor trafficking |
publishDate |
2014 |
url |
https://hdl.handle.net/10356/80929 http://hdl.handle.net/10220/19359 |
_version_ |
1725985680108027904 |