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The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4
Sitz JH, Baumgärtel K, Hämmerle B, Papadopoulos C, Hekerman P, Tejedor FJ, Becker W, Lutz B.. Neuroscience, 2008-10-01
Topic: Brain proteins, microglia and lab models
The dual-specific kinase DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) is the mammalian orthologue of the Drosophila minibrain (MNB) protein kinase and executes diverse roles in neuronal development and adult brain physiology. DYRK1A is overexpressed in Down syndrome (DS) and has recently been implicated in several neurodegenerative diseases. In an attempt to elucidate the molecular basis of its involvement in cognitive and neurodegeneration processes, we searched for novel proteins interacting with the kinase domain of DYRK1A in the adult mouse brain and identified septin 4 (SEPT4, also known as Pnutl2/CDCrel-2). SEPT4 is a member of the group III septin family of guanosine triphosphate hydrolases (GTPases), which has previously been found in neurofibrillary tangles of Alzheimer disease brains and in alpha-synuclein-positive cytoplasmic inclusions in Parkinson disease brains. In transfected mammalian cells, DYRK1A specifically interacts with and phosphorylates SEPT4. Phosphorylation of SEPT4 by DYRK1A was inhibited by harmine, which has recently been identified as the most specific inhibitor of DYRK1A. In support of a physiological relation in the brain, we found that Dyrk1A and Sept4 are co-expressed and co-localized in neocortical neurons. These findings suggest that SEPT4 is a substrate of DYRK1A kinase and thus provide a possible link for the involvement of DYRK1A in neurodegenerative processes and in DS neuropathologies.
Key findings
- In support of a physiological relation in the brain, we found that Dyrk1A and Sept4 are co-expressed and co-localized in neocortical neurons.
- These findings suggest that SEPT4 is a substrate of DYRK1A kinase and thus provide a possible link for the involvement of DYRK1A in neurodegenerative processes and in DS neuropathologies.
Why it matters
In transfected cells and mouse brain tissue, the DYRK1A kinase was found to interact with and phosphorylate the protein SEPT4, which has been found in neurofibrillary tangles of Alzheimer's disease brains. This is a laboratory study suggesting a possible link to neurodegeneration, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 42/100
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 (Neuroscience) |
| Journal's citation record | 3 / 4 | Neuroscience: journal h-index 370 (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 | 4 / 7 | Cited 79 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Beat Lutz: h-index 101 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | ETH Zurich: institution h-index 1,286 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18938227) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Sitz, J. H., Baumgärtel, K., Hämmerle, B., Papadopoulos, C., Hekerman, P., Tejedor, F. J., et al. (2008). The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience. https://doi.org/10.1016/j.neuroscience.2008.09.034
Vancouver
Sitz JH, Baumgärtel K, Hämmerle B, Papadopoulos C, Hekerman P, Tejedor FJ, et al. The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience. 2008. doi:10.1016/j.neuroscience.2008.09.034. PMID: 18938227.
BibTeX
@article{sitz2008-18938227,
author = {Sitz, J. H. and Baumgärtel, K. and Hämmerle, B. and Papadopoulos, C. and Hekerman, P. and Tejedor, F. J. and Becker, W. and Lutz, B.},
title = {{The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4}},
journal = {Neuroscience},
year = {2008},
doi = {10.1016/j.neuroscience.2008.09.034},
pmid = {18938227},
url = {https://doi.org/10.1016/j.neuroscience.2008.09.034}
}
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