The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson’s disease
Open accessAbstract
Significance: Determining the role for LRRK2, the most common Parkinson’s disease (PD) gene in neurons has been a challenge for the field. Combining interaction data from an unbiased screen in flies and a conserved physical relationship, we show that LRRK2 binds and phosphorylates the actin remodeling protein WAVE2 specifically in myeloid cells. Furthermore, we demonstrate that this relationship is important for WAVE2 stability and the dynamics of the phagocytic response. Finally, we provide evidence that in both mammalian cocultures, flies, and a murine model of PD that LRRK2s action on WAVE2 may be important for neuronal survival. This work supports the role for LRRK2 in immune-signaling and the role for the immune system in the pathogenesis and progression of PD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This complex regulates actin cytoskeleton organization and participates in cytokinesis, migration, endocytosis, and phagocytosis (14, 15).”
From Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An LRRK2 kinase inhibitor or an ARP2/3 inhibitor prevents microglial activation and neurotoxicity in vitro169,170, suggesting the involvement of the LRRK2-WAVE2 pathway in microglia in PD pathogenesis.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“LRRK2 binds and phosphorylates mouse WAVE2 at Thr470 (Thr471 in human WAVE2, Fig. 3b), stabilizing and preventing the proteasomal degradation of WAVE2, whereas LRRK2 does not interact with WAVE1169.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Macrophages or microglia isolated from PD patients or LRRK2-G2019S mice display increased phosphorylation at Thr470 on WAVE2 and enhanced phagocytic responses, but LRRK2 deletion causes the opposite effects.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“WAVE2 levels are also reduced in primary microglia and bone marrow-derived macrophages from LRRK2 KO mice.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
The cited source says what the claim attributes to it.
In the citing paper
“However, an increase in WAVE2 expression was observed in microglia and macrophages from LRRK2-G2019S knock-in mice169.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
The cited source says what the claim attributes to it.
In the citing paper
“In addition, WAVE2 and its phosphorylation are involved in LRRK2-G2019S-induced dopaminergic neuronal death in macrophage and midbrain cocultures.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
The cited source says what the claim attributes to it.
In the citing paper
“In BV2 microglia, LRRK2 knockdown reduces the level of WAVE2 but not the levels of WAVE1 and WAVE3.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, WAVE2 knockdown in mice and Scar knockdown in Drosophila ameliorate LRRK2-G2019S-induced dopaminergic neuron loss169.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [169]
The cited source says what the claim attributes to it.
In the citing paper
“Recently, WAVE2 was found to be directly modulated by leucine rich repeat kinase 2 (LRRK2) in microglia, establishing a potentially pathogenic role in development of Parkinson disease [50].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., et al. (2008) · Nature Genetics · doi:10.1038/ng.175 · Cited by 2,593
Self-citationAloisi, F. (2001) · Glia · doi:10.1002/glia.1106 · Cited by 1,310
Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases
Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., et al. (2016) · eLife · doi:10.7554/elife.12813 · Cited by 1,042
Phagocytosis and the actin cytoskeleton
May, R. C., & Machesky, L. M. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.6.1061 · Cited by 715
Reciprocal Regulation between Resting Microglial Dynamics and Neuronal Activity In Vivo
Li, Y., Du, X.-F., Liu, C., Wen, Z., & Du, J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.10.027 · Cited by 590
IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling
Miki, H., Yamaguchi, H., Suetsugu, S., & Takenawa, T. (2000) · Nature · doi:10.1038/35047107 · Cited by 550
Structure and control of the actin regulatory WAVE complex
Chen, Z., Borek, D., Padrick, S. B., Gomez, T. S., Metlagel, Z., Ismail, A. M., Umetani, J., Billadeau, D. D., Otwinowski, Z., & Rosen, M. K. (2010) · Nature · doi:10.1038/nature09623 · Cited by 500
LRRK2 in Parkinson's disease: protein domains and functional insights
Mata, I. F., Wedemeyer, W. J., Farrer, M. J., Taylor, J. P., & Gallo, K. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.03.006 · Cited by 498
Research works printed but not linked: 1
- 10.1038/cdd.2012.166 · DOI
Cited by
Sorted by citations
Inflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels, T., De Schepper, S., & Hong, S. (2020) · Science · doi:10.1126/science.abb8587 · Cited by 412
Microglia and astrocyte dysfunction in parkinson's disease
Kam, T., Hinkle, J. T., Dawson, T. M., & Dawson, V. L. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105028 · Cited by 414
Phagocytosis in the Brain: Homeostasis and Disease
Galloway, D. A., Phillips, A. E. M., Owen, D. R., & Moore, C. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00790 · Cited by 319
Microglial phagocytosis of neurons in neurodegeneration, and its regulation
Butler, C. A., Popescu, A. S., Kitchener, E. J. A., Allendorf, D. H., Puigdellívol, M., & Brown, G. C. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15327 · Cited by 295
Metadata
- Authors
- Kim, K. S., Marcogliese, P. C., Yang, J., Callaghan, S. M., Resende, V., Abdel-Messih, E., Marras, C., Visanji, N. P., Huang, J., Schlossmacher, M. G., Trinkle-Mulcahy, L., Slack, R. S., Lang, A. E., Canadian Lrrk2 in Inflammation Team (CLINT), Park, D. S., Brown, E., Gibbings, D., Hayley, S., Park, D., Philpott, D. C., Rioux, J. D., Schlossmacher, M., & Schurr, E.
- Affiliations
- University of Ottawa (CA)
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada;
- University Health Network (CA)
- University of Toronto (CA)
- Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8M5, Canada;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-05-14
- Volume
- 115
- Issue
- 22
- Pages
- E5164-E5173
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5984500
- OpenAlex
- W2803478714
- Cited by
- 111
- References
- 63
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 12 · 2023: 10 · 2022: 23 · 2021: 15 · 2020: 16 · 2019: 15 · 2018: 5
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (148402)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- LRRK2, Parkinson's disease, WAVE2, myeloid cells, phagocytosis, actin cytoskeleton remodeling, protein phosphorylation, protein stability, immune signaling, neuronal survival
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Animals, Cell Line, Drosophila, Humans, Parkinson Disease, Signal Transduction, Microglia, Myeloid Cells, Wiskott-Aldrich Syndrome Protein Family, Mice, Cytophagocytosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
