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Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants
In Caenorhabditis elegans, the P4-ATPase TAT-1 and its chaperone, the Cdc50 family protein CHAT-1, maintain membrane phosphatidylserine (PS) asymmetry, which is required for membrane tubulation during endocytic sorting and recycling. Loss of tat-1 and chat-1 disrupts endocytic sorting, leading to de...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623637/ https://www.ncbi.nlm.nih.gov/pubmed/23427264 http://dx.doi.org/10.1091/mbc.E12-10-0730 |
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author | Li, Xin Chen, Baohui Yoshina, Sawako Cai, Tanxi Yang, Fuquan Mitani, Shohei Wang, Xiaochen |
author_facet | Li, Xin Chen, Baohui Yoshina, Sawako Cai, Tanxi Yang, Fuquan Mitani, Shohei Wang, Xiaochen |
author_sort | Li, Xin |
collection | PubMed |
description | In Caenorhabditis elegans, the P4-ATPase TAT-1 and its chaperone, the Cdc50 family protein CHAT-1, maintain membrane phosphatidylserine (PS) asymmetry, which is required for membrane tubulation during endocytic sorting and recycling. Loss of tat-1 and chat-1 disrupts endocytic sorting, leading to defects in both cargo recycling and degradation. In this study, we identified the C. elegans aspartyl aminopeptidase DNPP-1, loss of which suppresses the sorting and recycling defects in tat-1 mutants without reversing the PS asymmetry defect. We found that tubular membrane structures containing recycling cargoes were restored in dnpp-1 tat-1 double mutants and that these tubules overlap with RME-1–positive recycling endosomes. The restoration of the tubular structures in dnpp-1 tat-1 mutants requires normal functions of RAB-5, RAB-10, and RME-1. In tat-1 mutants, we observed alterations in membrane surface charge and targeting of positively charged proteins that were reversed by loss of dnpp-1. DNPP-1 displays a specific aspartyl aminopeptidase activity in vitro, and its enzymatic activity is required for its function in vivo. Our data reveal the involvement of an aminopeptidase in regulating endocytic sorting and recycling and suggest possible roles of peptide signaling and/or protein metabolism in these processes. |
format | Online Article Text |
id | pubmed-3623637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36236372013-06-30 Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants Li, Xin Chen, Baohui Yoshina, Sawako Cai, Tanxi Yang, Fuquan Mitani, Shohei Wang, Xiaochen Mol Biol Cell Articles In Caenorhabditis elegans, the P4-ATPase TAT-1 and its chaperone, the Cdc50 family protein CHAT-1, maintain membrane phosphatidylserine (PS) asymmetry, which is required for membrane tubulation during endocytic sorting and recycling. Loss of tat-1 and chat-1 disrupts endocytic sorting, leading to defects in both cargo recycling and degradation. In this study, we identified the C. elegans aspartyl aminopeptidase DNPP-1, loss of which suppresses the sorting and recycling defects in tat-1 mutants without reversing the PS asymmetry defect. We found that tubular membrane structures containing recycling cargoes were restored in dnpp-1 tat-1 double mutants and that these tubules overlap with RME-1–positive recycling endosomes. The restoration of the tubular structures in dnpp-1 tat-1 mutants requires normal functions of RAB-5, RAB-10, and RME-1. In tat-1 mutants, we observed alterations in membrane surface charge and targeting of positively charged proteins that were reversed by loss of dnpp-1. DNPP-1 displays a specific aspartyl aminopeptidase activity in vitro, and its enzymatic activity is required for its function in vivo. Our data reveal the involvement of an aminopeptidase in regulating endocytic sorting and recycling and suggest possible roles of peptide signaling and/or protein metabolism in these processes. The American Society for Cell Biology 2013-04-15 /pmc/articles/PMC3623637/ /pubmed/23427264 http://dx.doi.org/10.1091/mbc.E12-10-0730 Text en © 2013 Li et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Li, Xin Chen, Baohui Yoshina, Sawako Cai, Tanxi Yang, Fuquan Mitani, Shohei Wang, Xiaochen Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title | Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title_full | Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title_fullStr | Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title_full_unstemmed | Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title_short | Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants |
title_sort | inactivation of caenorhabditis elegans aminopeptidase dnpp-1 restores endocytic sorting and recycling in tat-1 mutants |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623637/ https://www.ncbi.nlm.nih.gov/pubmed/23427264 http://dx.doi.org/10.1091/mbc.E12-10-0730 |
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