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The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period
Drosophila Double-time (DBT) phosphorylates the circadian protein Period (PER). The period-altering mutation tau, identified in hamster casein kinase I (CKIε) and created in Drosophila DBT, has been shown to shorten the circadian period in flies, as it does in hamsters. Since CKI often phosphorylate...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412653/ https://www.ncbi.nlm.nih.gov/pubmed/30769795 http://dx.doi.org/10.3390/ijms20040813 |
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author | Venkatesan, Anandakrishnan Fan, Jin-Yuan Bouyain, Samuel Price, Jeffrey L. |
author_facet | Venkatesan, Anandakrishnan Fan, Jin-Yuan Bouyain, Samuel Price, Jeffrey L. |
author_sort | Venkatesan, Anandakrishnan |
collection | PubMed |
description | Drosophila Double-time (DBT) phosphorylates the circadian protein Period (PER). The period-altering mutation tau, identified in hamster casein kinase I (CKIε) and created in Drosophila DBT, has been shown to shorten the circadian period in flies, as it does in hamsters. Since CKI often phosphorylates downstream of previously phosphorylated residues and the tau amino acid binds a negatively charged ion in X-ray crystal structures, this amino acid has been suggested to contribute to a phosphate recognition site for the substrate. Alternatively, the tau amino acid may affect a nuclear localization signal (NLS) with which it interacts. We mutated the residues that were close to or part of the phosphate recognition site or NLS. Flies expressing DBT with mutations of amino acids close to or part of either of these motifs produced a shortening of period, suggesting that a domain, including the phosphate recognition site or the NLS, can be mutated to produce the short period phenotype. Mutation of residues affecting internally placed residues produced a longer period, suggesting that a specific domain on the surface of the kinase might generate an interaction with a substrate or regulator, with short periods produced when the interaction is disrupted. |
format | Online Article Text |
id | pubmed-6412653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64126532019-04-05 The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period Venkatesan, Anandakrishnan Fan, Jin-Yuan Bouyain, Samuel Price, Jeffrey L. Int J Mol Sci Article Drosophila Double-time (DBT) phosphorylates the circadian protein Period (PER). The period-altering mutation tau, identified in hamster casein kinase I (CKIε) and created in Drosophila DBT, has been shown to shorten the circadian period in flies, as it does in hamsters. Since CKI often phosphorylates downstream of previously phosphorylated residues and the tau amino acid binds a negatively charged ion in X-ray crystal structures, this amino acid has been suggested to contribute to a phosphate recognition site for the substrate. Alternatively, the tau amino acid may affect a nuclear localization signal (NLS) with which it interacts. We mutated the residues that were close to or part of the phosphate recognition site or NLS. Flies expressing DBT with mutations of amino acids close to or part of either of these motifs produced a shortening of period, suggesting that a domain, including the phosphate recognition site or the NLS, can be mutated to produce the short period phenotype. Mutation of residues affecting internally placed residues produced a longer period, suggesting that a specific domain on the surface of the kinase might generate an interaction with a substrate or regulator, with short periods produced when the interaction is disrupted. MDPI 2019-02-14 /pmc/articles/PMC6412653/ /pubmed/30769795 http://dx.doi.org/10.3390/ijms20040813 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Venkatesan, Anandakrishnan Fan, Jin-Yuan Bouyain, Samuel Price, Jeffrey L. The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title | The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title_full | The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title_fullStr | The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title_full_unstemmed | The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title_short | The Circadian tau Mutation in Casein Kinase 1 Is Part of a Larger Domain That Can Be Mutated to Shorten Circadian Period |
title_sort | circadian tau mutation in casein kinase 1 is part of a larger domain that can be mutated to shorten circadian period |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412653/ https://www.ncbi.nlm.nih.gov/pubmed/30769795 http://dx.doi.org/10.3390/ijms20040813 |
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