Age-related guanine nucleotide exchange factor, mouse Zizimin2, induces filopodia in bone marrow-derived dendritic cells
Open accessAbstract
Background: We recently isolated and identified Zizimin2 as a functional factor that is highly expressed in murine splenic germinal center B cells after immunization with T-cell-dependent antigen. Zizimin2 was revealed to be a new family member of Dock (dedicator of cytokinesis), Dock11, which is the guanine nucleotide exchange factor for Cdc42, a low-molecular-weight GTPase. However, the molecular function of Zizimin2 in acquired immunity has not been elucidated. Results: In this study, we show that the protein expression of Zizimin2, which is also restricted to lymphoid tissues and lymphocytes, is reduced in aged mice. Over-expression of full-length Zizimin2 induced filopodial formation in 293T cells, whereas expression of CZH2 domain inhibited it. Stimulation of Fcγ receptor and Toll-like receptor 4 triggered Zizimin2 up-regulation and Cdc42 activation in bone marrow-derived dendritic cells. Conclusions: These data suggest that Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration.
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DOCK11 expression decreases in mouse lymphoid tissue.
“Expression was observed to decrease in mouse lymphoid tissue, where it was reportedly involved in structural remodeling such as filopodial formation (129).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [129]
The Results section (“Zizimin2 is down-regulated in aged mice”; page unavailable) reports lower DOCK11/Zizimin2 expression in aged mouse spleen than in young mouse spleen. The claim omits that age comparison and broadens the finding from spleen to mouse lymphoid tissue generally. The Discussion links Zizimin2 to filopodial formation in bone marrow-derived dendritic cells, rather than demonstrating that process throughout lymphoid tissue. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDOCK11 is involved in structural remodeling such as filopodial formation.
“Expression was observed to decrease in mouse lymphoid tissue, where it was reportedly involved in structural remodeling such as filopodial formation (129).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [129]
DOCK11 is implicated in aging processes.
“Similar to DOCK10, several studies have implicated DOCK11 in aging processes.”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [129]
DOCK11 is linked to Fcγ and TLR4 receptor engagement.
“It was also linked to Fcγ and TLR4 receptor engagement.”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [129]
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Cites
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Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller, N., Irani-Tehrani, M., Kiosses, W. B., Del Pozo, M. A., & Schwartz, M. A. (2002) · Nature Cell Biology · doi:10.1038/ncb835 · Cited by 171 · see citing works
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Sorted by citations
Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
“Expression was observed to decrease in mouse lymphoid tissue, where it was reportedly involved in structural remodeling such as filopodial formation (129).”
Background
- Authors
- Sakabe, I., Asai, A., Iijima, J., & Maruyama, M.
- Affiliations
- National Center for Geriatrics and Gerontology (JP)
- Corresponding author
- Maruyama, Mitsuo
- Venue
- Immunity & Ageing
- Published
- 2012-04-11
- Volume
- 9
- Issue
- 1
- Pages
- 2-2
- ISSN
- 1742-4933 (ISSN-L)
- PMC
- PMC3359169
- OpenAlex
- W2117516755
- Cited by
- 28
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 9 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 3 · 2013: 1
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Immunity & Ageing (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Center for Geriatrics and Gerontology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- guanine nucleotide exchange factor, Cdc42, filopodia, bone marrow-derived dendritic cells, aging, age-related immune decline, Fc gamma receptor, TLR4, cell migration, adaptive immunity
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