Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the...

Full description

Saved in:
Bibliographic Details
Main Authors: Jifeng Zhang, Yichen Yin, Zhisheng Ji, Zhenbin Cai, Bo Zhao, Jiong Li, Minghui Tan, Guoqing Guo
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2017/8197085
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849683257785843712
author Jifeng Zhang
Yichen Yin
Zhisheng Ji
Zhenbin Cai
Bo Zhao
Jiong Li
Minghui Tan
Guoqing Guo
author_facet Jifeng Zhang
Yichen Yin
Zhisheng Ji
Zhenbin Cai
Bo Zhao
Jiong Li
Minghui Tan
Guoqing Guo
author_sort Jifeng Zhang
collection DOAJ
description Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric Aβ-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric Aβ-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD.
format Article
id doaj-art-dc14bc7fb1c146d2bb50c733877693eb
institution DOAJ
issn 2090-5904
1687-5443
language English
publishDate 2017-01-01
publisher Wiley
record_format Article
series Neural Plasticity
spelling doaj-art-dc14bc7fb1c146d2bb50c733877693eb2025-08-20T03:23:57ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/81970858197085Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-βJifeng Zhang0Yichen Yin1Zhisheng Ji2Zhenbin Cai3Bo Zhao4Jiong Li5Minghui Tan6Guoqing Guo7Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Neurology, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaDepartment of Anatomy, Medical College of Jinan University, Guangzhou 510630, ChinaAmyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD), as oligomeric Aβ induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric Aβ-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric Aβ-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric Aβ-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD.http://dx.doi.org/10.1155/2017/8197085
spellingShingle Jifeng Zhang
Yichen Yin
Zhisheng Ji
Zhenbin Cai
Bo Zhao
Jiong Li
Minghui Tan
Guoqing Guo
Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
Neural Plasticity
title Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
title_full Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
title_fullStr Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
title_full_unstemmed Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
title_short Endophilin2 Interacts with GluA1 to Mediate AMPA Receptor Endocytosis Induced by Oligomeric Amyloid-β
title_sort endophilin2 interacts with glua1 to mediate ampa receptor endocytosis induced by oligomeric amyloid β
url http://dx.doi.org/10.1155/2017/8197085
work_keys_str_mv AT jifengzhang endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT yichenyin endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT zhishengji endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT zhenbincai endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT bozhao endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT jiongli endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT minghuitan endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb
AT guoqingguo endophilin2interactswithglua1tomediateampareceptorendocytosisinducedbyoligomericamyloidb