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Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration
Abstract
Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics, both of which are regulated by Rho family GTPases. Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement. The CDM family proteins, Caenorhabditis elegans CED-5, human DOCK180 and Drosophila melanogaster Myoblast City (MBC), are implicated to mediate membrane extension by functioning upstream of Rac. Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells, physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is indispensable for lymphocyte chemotaxis. DOCK2-deficient mice (DOCK2-/-) exhibited migration defects of T and B lymphocytes, but not of monocytes, in response to chemokines, resulting in several abnormalities including T lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. In DOCK2-/- lymphocytes, chemokine-induced Rac activation and actin polymerization were almost totally abolished. Thus, in lymphocyte migration DOCK2 functions as a central regulator that mediates cytoskeletal reorganization through Rac activation.
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“DOCK2 activates Rac but not Cdc42, whereas DOCK9 activates Cdc42 but not Rac (6,35,38).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [6]
In the citing paper
“Interestingly, the physiological activation of Rac by these GEFs requires their association with a regulatory protein ELMO1 (Engulfment and Motility) (6,33,34).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [6]
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Metadata
- Authors
- Fukui, Y., Hashimoto, O., Sanui, T., Oono, T., Koga, H., Abe, M., Inayoshi, A., Noda, M., Oike, M., Shirai, T., & Sasazuki, T.
- Affiliations
- Kyushu University (JP)
- Kurume University (JP)
- Juntendo University (JP)
- Corresponding author
- Shirai, Toshikazu
- ORCID
- Venue
- Nature
- Published
- 2001-08
- Volume
- 412
- Issue
- 6849
- Pages
- 826-831
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2022157262
- Cited by
- 449
- References
- 30
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 14 · 2018: 15 · 2017: 18 · 2016: 10 · 2015: 12 · 2014: 23 · 2013: 21 · 2012: 22
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Michigan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- DOCK2, lymphocyte chemotaxis, lymphocyte migration, Rac activation, Rho GTPases, actin polymerization, cytoskeletal remodeling, T cells, B cells, marginal zone B cells, lymphopenia, chemokines
- MeSH terms
- Animals, B-Lymphocytes, Carrier Proteins, Cell Line, Chemotaxis, Leukocyte, Cytoskeleton, Female, Hematopoietic Stem Cells, Immunologic Memory, Male, Mice, Inbred C57BL, Spleen, Stem Cells, T-Lymphocytes, Cytokines, Chemokines, CXC, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Mice, Chemokine CXCL12
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