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Cited by 77Alzheimer's disease research and treatmentsCellular transport and secretionNeuroscience and Neuropharmacology Research

A Function for EHD Family Proteins in Unidirectional Retrograde Dendritic Transport of BACE1 and Alzheimer’s Disease Aβ Production

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Buggia-Prévot, Virginie, Fernandez, Celia G., Udayar, Vinod, Vetrivel, Kulandaivelu S., Elie, Aureliane, Roseman, Jelita, Sasse, Verena A., Lefkow, Margaret +10 more·2013·Cell Reports
DOI 10.1016/j.celrep.2013.12.006PMC PMC3932704
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Abstract

Abnormal accumulation of β-secretase (BACE1) in dystrophic neurites and presynaptic β-amyloid (Aβ) production contribute to Alzheimer's disease pathogenesis. Little, however, is known about BACE1 sorting and dynamic transport in neurons. We investigated BACE1 trafficking in hippocampal neurons using live-cell imaging and selective labeling. We report that transport vesicles containing internalized BACE1 in dendrites undergo exclusive retrograde transport toward the soma, whereas they undergo bidirectional transport in axons. Unidirectional dendritic transport requires Eps15-homology-domain-containing (EHD) 1 and 3 protein function. Furthermore, loss of EHD function compromises dynamic axonal transport and overall BACE1 levels in axons. EHD1/3 colocalize with BACE1 and APP β-C-terminal fragments in hippocampal mossy fiber terminals, and their depletion in neurons significantly attenuates Aβ levels. These results demonstrate unidirectional endocytic transport of a dendritic cargo and reveal a role for EHD proteins in neuronal BACE1 transcytosis and Aβ production, processes that are highly relevant for Alzheimer's disease.

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  • Loss of EHD1 function compromised recycling and axonal sorting of internalized BACE1, thereby reducing Ab production.

    “Loss of EHD1 function compromised the recycling and axonal sorting of the internalized BACE1, thereby reducing Ab production (42).”

    From BIN1 regulates BACE1 intracellular trafficking and amyloid-β production (2016) · cites this paper as [42]

    The Results section reports that impaired EHD1 function reduced axonal sorting of internalized BACE1, and the Introduction reports that loss of EHD1 expression reduced Aβ production in hippocampal neurons. But the Results do not establish compromised BACE1 recycling: internalized BACE1 still reached recycling endosomes, and its steady-state dendritic surface localization was not significantly affected. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Among known BIN1-binding proteins, EHD family proteins play a role in trafficking of internalized BACE1 in neurons.

    “It is noteworthy to mention that among the known BIN1-binding proteins, EHD family proteins play a role in the trafficking of internalized BACE1 in neurons (42).”

    From BIN1 regulates BACE1 intracellular trafficking and amyloid-β production (2016) · cites this paper as [42]

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Authors
Buggia-Prévot, V., Fernandez, C. G., Udayar, V., Vetrivel, K. S., Elie, A., Roseman, J., Sasse, V. A., Lefkow, M., Meckler, X., Bhattacharyya, S., George, M., Kar, S., Bindokas, V. P., Parent, A. T., Rajendran, L., Band, H., Vassar, R., & Thinakaran, G.
Affiliations
  • University of Chicago (US)
  • University of Zurich (CH)
  • University of Alberta (CA)
  • Fred and Pamela Buffett Cancer Center (US)
  • Northwestern University (US)
Corresponding author
Thinakaran, Gopal
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2013-12
Volume
5
Issue
6
Pages
1552-1563
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2013.12.006
PMC
PMC3932704
OpenAlex
W1974507908
Cited by
77
References
1
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 8 · 2016: 11 · 2015: 11 · 2014: 10 · 2013: 1
FWCI
7.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Institutes of Health (1s10od010649-01)
  • National Institute on Aging (AG030142, RF1AG022560, R01AG019070, AG022560, R01AG030142, R01AG022560, AG019070, R01AG021495, AG021495)
  • National Cancer Institute (CA 116552, R01CA099163, CA105489, R01CA105489, CA 87986, R01CA087986, R01CA116552, CA 99163)
  • National Institute of General Medical Sciences (GM07839-30, T32GM007839)
  • National Institute of Neurological Disorders and Stroke (R01NS055223, NS055223)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
BACE1, EHD1, EHD3, Eps15 homology domain, dendritic transport, axonal transport, amyloid-beta production, Alzheimer's disease, endocytic transport, transcytosis, mossy fiber terminals, hippocampal neurons, protein trafficking
MeSH terms
Alzheimer Disease, Animals, Axonal Transport, Carrier Proteins, Cells, Cultured, Dendrites, HeLa Cells, Hippocampus, Humans, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Protein Transport, Vesicular Transport Proteins, Mice, Amyloid Precursor Protein Secretases, HEK293 Cells

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