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: Loo, Li Shen, Tang, Ning, Al-Haddawi, Muthafar, Stewart Dawe, Gavin, Hong, Wanjin
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2014
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Online Access:https://hdl.handle.net/10356/80929
http://hdl.handle.net/10220/19359
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Institution: Nanyang Technological University
Language: English
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Medicine
spellingShingle 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
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