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Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata

Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), t...

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Autores principales: Liu, Huimin, Sang, Shaoming, Lu, Yuan, Wang, Zhongfeng, Yu, Xiang, Zhong, Chunjiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509691/
https://www.ncbi.nlm.nih.gov/pubmed/28706281
http://dx.doi.org/10.1038/s41598-017-05476-w
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author Liu, Huimin
Sang, Shaoming
Lu, Yuan
Wang, Zhongfeng
Yu, Xiang
Zhong, Chunjiu
author_facet Liu, Huimin
Sang, Shaoming
Lu, Yuan
Wang, Zhongfeng
Yu, Xiang
Zhong, Chunjiu
author_sort Liu, Huimin
collection PubMed
description Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have been associated with developmental neurological disorders, including microcephaly and Leigh syndrome. However, little is known about how thiamine metabolism regulates neuronal morphology at the cellular level. Here, using primary rat hippocampal neuronal cultures, we showed that reducing the expression of Tpk1, Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite complexity, as measured by total dendritic branch tip number (TDBTN) and total dendritic branch length (TDBL). The specificity of the RNAi effects were verified by overexpression of RNAi resistant human constructs. Importantly, changes in both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating coordinated regulation of soma and dendrite growth by thiamine. The requirement of thiamine metabolism for coordinated somata and dendrite growth is highly consistent with the microcephaly and neurodegenerative phenotypes observed in thiamine loss-of-function diseases.
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spelling pubmed-55096912017-07-17 Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata Liu, Huimin Sang, Shaoming Lu, Yuan Wang, Zhongfeng Yu, Xiang Zhong, Chunjiu Sci Rep Article Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have been associated with developmental neurological disorders, including microcephaly and Leigh syndrome. However, little is known about how thiamine metabolism regulates neuronal morphology at the cellular level. Here, using primary rat hippocampal neuronal cultures, we showed that reducing the expression of Tpk1, Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite complexity, as measured by total dendritic branch tip number (TDBTN) and total dendritic branch length (TDBL). The specificity of the RNAi effects were verified by overexpression of RNAi resistant human constructs. Importantly, changes in both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating coordinated regulation of soma and dendrite growth by thiamine. The requirement of thiamine metabolism for coordinated somata and dendrite growth is highly consistent with the microcephaly and neurodegenerative phenotypes observed in thiamine loss-of-function diseases. Nature Publishing Group UK 2017-07-13 /pmc/articles/PMC5509691/ /pubmed/28706281 http://dx.doi.org/10.1038/s41598-017-05476-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Huimin
Sang, Shaoming
Lu, Yuan
Wang, Zhongfeng
Yu, Xiang
Zhong, Chunjiu
Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_full Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_fullStr Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_full_unstemmed Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_short Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_sort thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509691/
https://www.ncbi.nlm.nih.gov/pubmed/28706281
http://dx.doi.org/10.1038/s41598-017-05476-w
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