CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration
Open accessAbstract
The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.
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The physiological activation of Rac by DOCK2 and DOCK180 requires their association with a regulatory protein ELMO1.
“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 [33]
The Rac-GEF activity section reports that ELMO1 associates with Dock180 and increases Dock180-dependent Rac-GTP loading in transfected cells. It also reports Rac-GTP loading with Dock180 alone, so it does not establish that ELMO1 association is required for physiological activation. The CED-12/ELMO and CED-5/Dock180 Connection section says interaction between Dock-2 and ELMO proteins remains to be tested. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDOCK1 has reported roles in cell migration, invasion, and phagocytosis.
“It has reported roles in cell migration, invasion, and phagocytosis (48, 51, 52, 53, 54).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [52]
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Research works printed but not linked: 1
- Tosello-Trampont, A., Brugnera, E., and Ravichandran, K.S. (2001). Evidence for a conserved role for CrkII and Rac in engulfment of apoptotic cells. J. Biol. Chem., in press.
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- Authors
- Gumienny, T. L., Brugnera, E., Tosello-Trampont, A.-C., Kinchen, J. M., Haney, L. B., Nishiwaki, K., Walk, S. F., Nemergut, M. E., Macara, I. G., Francis, R., Schedl, T., Qin, Y., Van Aelst, L., Hengartner, M. O., & Ravichandran, K. S.
- Affiliations
- State University of New York (US)
- University of Virginia (US)
- NEC (Japan) (JP)
- Washington University in St. Louis (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Hengartner, Michael O.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 107
- Issue
- 1
- Pages
- 27-41
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2071481601
- Cited by
- 568
- References
- 0
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 8 · 2023: 18 · 2022: 22 · 2021: 18 · 2020: 23 · 2019: 24 · 2018: 24 · 2017: 13 · 2016: 30 · 2015: 24 · 2014: 23 · 2013: 22 · 2012: 25
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health (2r01gm052540-06)
- National Institute of General Medical Sciences (R01GM063310, GM 63310, GM52540)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ELMO1, CrkII, DOCK180, Rac1, phagocytosis, cell migration, cytoskeletal rearrangement, cell shape changes, Caenorhabditis elegans
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Cell Movement, Cytoskeletal Proteins, Cytoskeleton, Flow Cytometry, Gonads, Humans, Male, Microscopy, Fluorescence, Molecular Sequence Data, Phagocytosis, Protein Kinases, Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Tissue Distribution, Signal Transduction, Helminth Proteins, Sequence Alignment, Caenorhabditis elegans, Genes, Helminth, Genes, Reporter, rac GTP-Binding Proteins, Cell Surface Extensions, Caenorhabditis elegans Proteins, Animals, Genetically Modified, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-crk, Apoptosis Regulatory Proteins, Mice
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