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Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac,...

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Autores principales: Hurwitz, Michael E, Vanderzalm, Pamela J, Bloom, Laird, Goldman, Julia, Garriga, Gian, Horvitz, H. Robert
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672617/
https://www.ncbi.nlm.nih.gov/pubmed/19402756
http://dx.doi.org/10.1371/journal.pbio.1000099
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author Hurwitz, Michael E
Vanderzalm, Pamela J
Bloom, Laird
Goldman, Julia
Garriga, Gian
Horvitz, H. Robert
author_facet Hurwitz, Michael E
Vanderzalm, Pamela J
Bloom, Laird
Goldman, Julia
Garriga, Gian
Horvitz, H. Robert
author_sort Hurwitz, Michael E
collection PubMed
description The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac, and acts to rearrange the cytoskeleton of the engulfing cell. The other pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Although many components required for engulfment have been identified, little is known about inhibition of engulfment. The tyrosine kinase Abl regulates the actin cytoskeleton in mammals and Drosophila in multiple ways. For example, Abl inhibits cell migration via phosphorylation of CrkII. We tested whether ABL-1, the C. elegans ortholog of Abl, inhibits the CED-2 CrkII-dependent engulfment of apoptotic cells. Our genetic studies indicate that ABL-1 inhibits apoptotic cell engulfment, but not through CED-2 CrkII, and instead acts in parallel to the two known engulfment pathways. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The loss of ABL-1 function partially restores normal DTC migration in the CED-10 Rac pathway mutants. We found that ABI-1 the C. elegans homolog of mammalian Abi (Abl interactor) proteins, is required for engulfment of apoptotic cells and proper DTC migration. Like Abl, Abi proteins are cytoskeletal regulators. ABI-1 acts in parallel to the two known engulfment pathways, likely downstream of ABL-1. ABL-1 and ABI-1 interact physically in vitro. We propose that ABL-1 opposes the engulfment of apoptotic cells by inhibiting ABI-1 via a pathway that is distinct from the two known engulfment pathways.
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spelling pubmed-26726172009-04-28 Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans Hurwitz, Michael E Vanderzalm, Pamela J Bloom, Laird Goldman, Julia Garriga, Gian Horvitz, H. Robert PLoS Biol Research Article The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac, and acts to rearrange the cytoskeleton of the engulfing cell. The other pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Although many components required for engulfment have been identified, little is known about inhibition of engulfment. The tyrosine kinase Abl regulates the actin cytoskeleton in mammals and Drosophila in multiple ways. For example, Abl inhibits cell migration via phosphorylation of CrkII. We tested whether ABL-1, the C. elegans ortholog of Abl, inhibits the CED-2 CrkII-dependent engulfment of apoptotic cells. Our genetic studies indicate that ABL-1 inhibits apoptotic cell engulfment, but not through CED-2 CrkII, and instead acts in parallel to the two known engulfment pathways. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The loss of ABL-1 function partially restores normal DTC migration in the CED-10 Rac pathway mutants. We found that ABI-1 the C. elegans homolog of mammalian Abi (Abl interactor) proteins, is required for engulfment of apoptotic cells and proper DTC migration. Like Abl, Abi proteins are cytoskeletal regulators. ABI-1 acts in parallel to the two known engulfment pathways, likely downstream of ABL-1. ABL-1 and ABI-1 interact physically in vitro. We propose that ABL-1 opposes the engulfment of apoptotic cells by inhibiting ABI-1 via a pathway that is distinct from the two known engulfment pathways. Public Library of Science 2009-04 2009-04-28 /pmc/articles/PMC2672617/ /pubmed/19402756 http://dx.doi.org/10.1371/journal.pbio.1000099 Text en © 2009 Hurwitz et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hurwitz, Michael E
Vanderzalm, Pamela J
Bloom, Laird
Goldman, Julia
Garriga, Gian
Horvitz, H. Robert
Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title_full Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title_fullStr Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title_full_unstemmed Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title_short Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans
title_sort abl kinase inhibits the engulfment of apopotic cells in caenorhabditis elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672617/
https://www.ncbi.nlm.nih.gov/pubmed/19402756
http://dx.doi.org/10.1371/journal.pbio.1000099
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