The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo
Open accessAbstract
Apoptosis and the subsequent clearance of dying cells occurs throughout development and adult life in many tissues. Failure to promptly clear apoptotic cells has been linked to many diseases. ELMO1 is an evolutionarily conserved cytoplasmic engulfment protein that functions downstream of the phosphatidylserine receptor BAI1, and, along with DOCK1 and the GTPase RAC1, promotes internalization of the dying cells. Here we report the generation of ELMO1-deficient mice, which we found to be unexpectedly viable and grossly normal. However, they had a striking testicular pathology, with disrupted seminiferous epithelium, multinucleated giant cells, uncleared apoptotic germ cells and decreased sperm output. Subsequent in vitro and in vivo analyses revealed a crucial role for ELMO1 in the phagocytic clearance of apoptotic germ cells by Sertoli cells lining the seminiferous epithelium. The engulfment receptor BAI1 and RAC1 (upstream and downstream of ELMO1, respectively) were also important for Sertoli-cell-mediated engulfment. Collectively, these findings uncover a selective requirement for ELMO1 in Sertoli-cell-mediated removal of apoptotic germ cells and make a compelling case for a relationship between engulfment and tissue homeostasis in vivo.
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Cites
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Autoimmune Disease and Impaired Uptake of Apoptotic Cells in MFG-E8-Deficient Mice
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Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
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Self-citationTyro-3 family receptors are essential regulators of mammalian spermatogenesis
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Arandjelovic, S., & Ravichandran, K. S. (2015) · Nature Immunology · doi:10.1038/ni.3253 · Cited by 959
Self-citationBeginnings of a Good Apoptotic Meal: The Find-Me and Eat-Me Signaling Pathways
Ravichandran, K. S. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.004 · Cited by 559
Self-citationInternational Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
Hamann, J., Aust, G., Araç, D., Engel, F. B., Formstone, C., Fredriksson, R., Hall, R. A., Harty, B. L., Kirchhoff, C., Knapp, B., et al. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009647 · Cited by 486
Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology
Morioka, S., Maueröder, C., & Ravichandran, K. S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.018 · Cited by 391
Self-citationThe Dynamics of Apoptotic Cell Clearance
Elliott, M. R., & Ravichandran, K. S. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.06.029 · Cited by 319
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Metadata
- Authors
- Elliott, M. R., Zheng, S., Park, D., Woodson, R. I., Reardon, M. A., Juncadella, I. J., Kinchen, J. M., Zhang, J., Lysiak, J. J., & Ravichandran, K. S.
- Venue
- Nature
- Published
- 2010-09
- Volume
- 467
- Issue
- 7313
- Pages
- 333-337
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2058413014
- Cited by
- 174
- References
- 5
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
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- Elliott, M. R., Zheng, S., Park, D., Woodson, R. I., Reardon, M. A., Juncadella, I. J., Kinchen, J. M., Zhang, J., Lysiak, J. J., & Ravichandran, K. S. (2010). Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature. https://doi.org/10.1038/nature09356
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