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Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4)
Tetrahydrobiopterin (BH4) is the natural cofactor of several enzymes widely distributed among eukaryotes, including aromatic amino acid hydroxylases (AAAHs), nitric oxide synthases (NOSs), and alkylglycerol monooxygenase (AGMO). We show here that the nematode Caenorhabditis elegans, which has three...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Genetics Society of America
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423366/ https://www.ncbi.nlm.nih.gov/pubmed/25808955 http://dx.doi.org/10.1534/genetics.114.174110 |
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author | Loer, Curtis M. Calvo, Ana C. Watschinger, Katrin Werner-Felmayer, Gabriele O’Rourke, Delia Stroud, Dave Tong, Amy Gotenstein, Jennifer R. Chisholm, Andrew D. Hodgkin, Jonathan Werner, Ernst R. Martinez, Aurora |
author_facet | Loer, Curtis M. Calvo, Ana C. Watschinger, Katrin Werner-Felmayer, Gabriele O’Rourke, Delia Stroud, Dave Tong, Amy Gotenstein, Jennifer R. Chisholm, Andrew D. Hodgkin, Jonathan Werner, Ernst R. Martinez, Aurora |
author_sort | Loer, Curtis M. |
collection | PubMed |
description | Tetrahydrobiopterin (BH4) is the natural cofactor of several enzymes widely distributed among eukaryotes, including aromatic amino acid hydroxylases (AAAHs), nitric oxide synthases (NOSs), and alkylglycerol monooxygenase (AGMO). We show here that the nematode Caenorhabditis elegans, which has three AAAH genes and one AGMO gene, contains BH4 and has genes that function in BH4 synthesis and regeneration. Knockout mutants for putative BH4 synthetic enzyme genes lack the predicted enzymatic activities, synthesize no BH4, and have indistinguishable behavioral and neurotransmitter phenotypes, including serotonin and dopamine deficiency. The BH4 regeneration enzymes are not required for steady-state levels of biogenic amines, but become rate limiting in conditions of reduced BH4 synthesis. BH4-deficient mutants also have a fragile cuticle and are generally hypersensitive to exogenous agents, a phenotype that is not due to AAAH deficiency, but rather to dysfunction in the lipid metabolic enzyme AGMO, which is expressed in the epidermis. Loss of AGMO or BH4 synthesis also specifically alters the sensitivity of C. elegans to bacterial pathogens, revealing a cuticular function for AGMO-dependent lipid metabolism in host–pathogen interactions. |
format | Online Article Text |
id | pubmed-4423366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-44233662015-05-08 Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) Loer, Curtis M. Calvo, Ana C. Watschinger, Katrin Werner-Felmayer, Gabriele O’Rourke, Delia Stroud, Dave Tong, Amy Gotenstein, Jennifer R. Chisholm, Andrew D. Hodgkin, Jonathan Werner, Ernst R. Martinez, Aurora Genetics Investigations Tetrahydrobiopterin (BH4) is the natural cofactor of several enzymes widely distributed among eukaryotes, including aromatic amino acid hydroxylases (AAAHs), nitric oxide synthases (NOSs), and alkylglycerol monooxygenase (AGMO). We show here that the nematode Caenorhabditis elegans, which has three AAAH genes and one AGMO gene, contains BH4 and has genes that function in BH4 synthesis and regeneration. Knockout mutants for putative BH4 synthetic enzyme genes lack the predicted enzymatic activities, synthesize no BH4, and have indistinguishable behavioral and neurotransmitter phenotypes, including serotonin and dopamine deficiency. The BH4 regeneration enzymes are not required for steady-state levels of biogenic amines, but become rate limiting in conditions of reduced BH4 synthesis. BH4-deficient mutants also have a fragile cuticle and are generally hypersensitive to exogenous agents, a phenotype that is not due to AAAH deficiency, but rather to dysfunction in the lipid metabolic enzyme AGMO, which is expressed in the epidermis. Loss of AGMO or BH4 synthesis also specifically alters the sensitivity of C. elegans to bacterial pathogens, revealing a cuticular function for AGMO-dependent lipid metabolism in host–pathogen interactions. Genetics Society of America 2015-05 2015-03-24 /pmc/articles/PMC4423366/ /pubmed/25808955 http://dx.doi.org/10.1534/genetics.114.174110 Text en Copyright © 2015 Loer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Loer, Curtis M. Calvo, Ana C. Watschinger, Katrin Werner-Felmayer, Gabriele O’Rourke, Delia Stroud, Dave Tong, Amy Gotenstein, Jennifer R. Chisholm, Andrew D. Hodgkin, Jonathan Werner, Ernst R. Martinez, Aurora Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title | Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title_full | Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title_fullStr | Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title_full_unstemmed | Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title_short | Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4) |
title_sort | cuticle integrity and biogenic amine synthesis in caenorhabditis elegans require the cofactor tetrahydrobiopterin (bh4) |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423366/ https://www.ncbi.nlm.nih.gov/pubmed/25808955 http://dx.doi.org/10.1534/genetics.114.174110 |
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