Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development
The term programmed cell death (PCD) was coined in 1965 to describe the loss of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. While it was subsequently demonstrated that this hormonally controlled death requires de novo gene expression, the signal transduction pathway that...
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doaj-6e20a39a5446453c84dd0260f7e8f79a2020-11-25T02:53:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00622547063Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During DevelopmentAnkur Sheel0Ankur Sheel1Rong Shao2Rong Shao3Rong Shao4Christine Brown5Joanne Johnson6Alexandra Hamilton7Danhui Sun8Danhui Sun9Julia Oppenheimer10Wendy Smith11Pablo E. Visconti12Pablo E. Visconti13Michele Markstein14Michele Markstein15Carol Bigelow16Lawrence M. Schwartz17Lawrence M. Schwartz18Department of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Pharmacology, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, Barnard College, Columbia University, New York, NY, United StatesDepartment of Biology, College of Science, Northeastern University, Boston, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, United StatesDepartment of Biology, University of Massachusetts Amherst, Amherst, MA, United StatesMolecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA, United StatesThe term programmed cell death (PCD) was coined in 1965 to describe the loss of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. While it was subsequently demonstrated that this hormonally controlled death requires de novo gene expression, the signal transduction pathway that couples hormone action to cell death is largely unknown. Using the ISMs from the tobacco hawkmoth Manduca sexta, we have found that Acheron/LARP6 mRNA is induced ∼1,000-fold on the day the muscles become committed to die. Acheron functions as a survival protein that protects cells until cell death is initiated at eclosion (emergence), at which point it becomes phosphorylated and degraded in response to the peptide Eclosion Hormone (EH). Acheron binds to a novel BH3-only protein that we have named BBH1 (BAD/BNIP3 homology 1). BBH1 accumulates on the day the ISMs become committed to die and is presumably liberated when Acheron is degraded. This is correlated with the release and rapid degradation of cytochrome c and the subsequent demise of the cell. RNAi experiments in the fruit fly Drosophila confirmed that loss of Acheron results in precocious ecdysial muscle death while targeting BBH1 prevents death altogether. Acheron is highly expressed in neurons and muscles in humans and drives metastatic processes in some cancers, suggesting that it may represent a novel survival protein that protects terminally differentiated cells and some cancers from death.https://www.frontiersin.org/article/10.3389/fcell.2020.00622/fullManduca sextaintersegmental muscleDrosophilaBADapoptosisautophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ankur Sheel Ankur Sheel Rong Shao Rong Shao Rong Shao Christine Brown Joanne Johnson Alexandra Hamilton Danhui Sun Danhui Sun Julia Oppenheimer Wendy Smith Pablo E. Visconti Pablo E. Visconti Michele Markstein Michele Markstein Carol Bigelow Lawrence M. Schwartz Lawrence M. Schwartz |
spellingShingle |
Ankur Sheel Ankur Sheel Rong Shao Rong Shao Rong Shao Christine Brown Joanne Johnson Alexandra Hamilton Danhui Sun Danhui Sun Julia Oppenheimer Wendy Smith Pablo E. Visconti Pablo E. Visconti Michele Markstein Michele Markstein Carol Bigelow Lawrence M. Schwartz Lawrence M. Schwartz Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development Frontiers in Cell and Developmental Biology Manduca sexta intersegmental muscle Drosophila BAD apoptosis autophagy |
author_facet |
Ankur Sheel Ankur Sheel Rong Shao Rong Shao Rong Shao Christine Brown Joanne Johnson Alexandra Hamilton Danhui Sun Danhui Sun Julia Oppenheimer Wendy Smith Pablo E. Visconti Pablo E. Visconti Michele Markstein Michele Markstein Carol Bigelow Lawrence M. Schwartz Lawrence M. Schwartz |
author_sort |
Ankur Sheel |
title |
Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development |
title_short |
Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development |
title_full |
Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development |
title_fullStr |
Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development |
title_full_unstemmed |
Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development |
title_sort |
acheron/larp6 is a survival protein that protects skeletal muscle from programmed cell death during development |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2020-07-01 |
description |
The term programmed cell death (PCD) was coined in 1965 to describe the loss of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. While it was subsequently demonstrated that this hormonally controlled death requires de novo gene expression, the signal transduction pathway that couples hormone action to cell death is largely unknown. Using the ISMs from the tobacco hawkmoth Manduca sexta, we have found that Acheron/LARP6 mRNA is induced ∼1,000-fold on the day the muscles become committed to die. Acheron functions as a survival protein that protects cells until cell death is initiated at eclosion (emergence), at which point it becomes phosphorylated and degraded in response to the peptide Eclosion Hormone (EH). Acheron binds to a novel BH3-only protein that we have named BBH1 (BAD/BNIP3 homology 1). BBH1 accumulates on the day the ISMs become committed to die and is presumably liberated when Acheron is degraded. This is correlated with the release and rapid degradation of cytochrome c and the subsequent demise of the cell. RNAi experiments in the fruit fly Drosophila confirmed that loss of Acheron results in precocious ecdysial muscle death while targeting BBH1 prevents death altogether. Acheron is highly expressed in neurons and muscles in humans and drives metastatic processes in some cancers, suggesting that it may represent a novel survival protein that protects terminally differentiated cells and some cancers from death. |
topic |
Manduca sexta intersegmental muscle Drosophila BAD apoptosis autophagy |
url |
https://www.frontiersin.org/article/10.3389/fcell.2020.00622/full |
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