Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons

Miao Sun, Chengyu Huang, Hui Wang, Huaye Zhang

Research output: Contribution to journalArticle

Abstract

The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons.

Original languageEnglish (US)
Pages (from-to)87-93
Number of pages7
JournalNeurobiology of Aging
Volume77
DOIs
StatePublished - May 1 2019

Fingerprint

Amyloid beta-Protein Precursor
Neurons
Amyloid
PDZ Domains
Amyloid Precursor Protein Secretases
Endosomes
Protein Transport
Dendrites
Organelles
Axons
Alzheimer Disease
Peptides
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • Neuroscience(all)
  • Developmental Biology

Cite this

@article{38f35a0df3ac4341ab825a80149f8697,
title = "Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons",
abstract = "The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons.",
author = "Miao Sun and Chengyu Huang and Hui Wang and Huaye Zhang",
year = "2019",
month = "5",
day = "1",
doi = "https://doi.org/10.1016/j.neurobiolaging.2019.01.023",
language = "English (US)",
volume = "77",
pages = "87--93",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons. / Sun, Miao; Huang, Chengyu; Wang, Hui; Zhang, Huaye.

In: Neurobiology of Aging, Vol. 77, 01.05.2019, p. 87-93.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons

AU - Sun, Miao

AU - Huang, Chengyu

AU - Wang, Hui

AU - Zhang, Huaye

PY - 2019/5/1

Y1 - 2019/5/1

N2 - The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons.

AB - The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the absence of Par3, there is an increase in the convergence between internalized APP and BACE1. In hippocampal neurons, loss of Par3 leads to increased APP and BACE1 convergence in axons but not in dendrites. This polarized convergence mainly occurs in retrograde or stalled axonal late endocytic organelles and is likely due to compartment-specific regulation of APP trafficking by Par3. Together, our data show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons.

UR - http://www.scopus.com/inward/record.url?scp=85061637227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061637227&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.neurobiolaging.2019.01.023

DO - https://doi.org/10.1016/j.neurobiolaging.2019.01.023

M3 - Article

VL - 77

SP - 87

EP - 93

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -