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Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
Lee J, Retamal C, Cuitiño L, Caruano-Yzermans A, Shin JE, van Kerkhof P, Marzolo MP, Bu G.. The Journal of biological chemistry, 2008-02-13
Topic: Brain proteins, microglia and lab models
Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease. Production of Abeta from APP is greatly affected by the subcellular localization and trafficking of APP. Here we have identified a novel intracellular adaptor protein, sorting nexin 17 (SNX17), that binds specifically to the APP cytoplasmic domain via the YXNPXY motif that has been shown previously to bind several cell surface adaptors, including Fe65 and X11.
Key findings
- Production of Abeta from APP is greatly affected by the subcellular localization and trafficking of APP.
- Here we have identified a novel intracellular adaptor protein, sorting nexin 17 (SNX17), that binds specifically to the APP cytoplasmic domain via the YXNPXY motif that has been shown previously to bind several cell surface adaptors, including Fe65 and X11.
- Overexpression of a dominant-negative mutant of SNX17 and RNA interference knockdown of endogenous SNX17 expression both reduced steady-state levels of APP with a concomitant increase in Abeta production.
- RNA interference knockdown of SNX17 also decreased APP half-life, which led to the decreased steady-state levels of APP.
Why it matters
This study identified sorting nexin 17 (SNX17) as an adaptor protein that binds amyloid precursor protein and affects its trafficking and processing in early endosomes. It is laboratory cell work on basic biology and reports no treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 164 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.2 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 5.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Guojun Bu: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18276590) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m800642200
- PubMed: 18276590
- Original source →
- Free full text: Journal of Biological Chemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Lee, J., Retamal, C., Cuitiño, L., Caruano-Yzermans, A., Shin, J. E., van Kerkhof, P., et al. (2008). Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m800642200
Vancouver
Lee J, Retamal C, Cuitiño L, Caruano-Yzermans A, Shin JE, van Kerkhof P, et al. Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. The Journal of biological chemistry. 2008. doi:10.1074/jbc.m800642200. PMID: 18276590.
BibTeX
@article{lee2008-18276590,
author = {Lee, J. and Retamal, C. and Cuitiño, L. and Caruano-Yzermans, A. and Shin, J. E. and van Kerkhof, P. and Marzolo, M. P. and Bu, G.},
title = {{Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes}},
journal = {The Journal of biological chemistry},
year = {2008},
doi = {10.1074/jbc.m800642200},
pmid = {18276590},
url = {https://doi.org/10.1074/jbc.m800642200}
}
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