BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus

Abstract Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	S. M. van Liempd, D. Cabrera, F. Y. Lee, E. González, E. C. Dell’Angelica, C. A. Ghiani, J. M. Falcon-Perez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b75ff7c17f24ce9892424db41d9bd69
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3b75ff7c17f24ce9892424db41d9bd69
record_format	dspace
spelling	oai:doaj.org-article:3b75ff7c17f24ce9892424db41d9bd692021-12-02T16:06:57ZBLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus10.1038/s41598-017-05465-z2045-2322https://doaj.org/article/3b75ff7c17f24ce9892424db41d9bd692017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05465-zhttps://doaj.org/toc/2045-2322Abstract Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by BLOC-1 deficiency in pallid mice, which carry a null mutation in the Bloc1s6 gene encoding an essential component of this complex. The metabolome of the hippocampus of pallid mice was analysed using an untargeted, liquid chromatography-coupled mass spectrometric approach. After data pre-treatment, statistical analysis and pathway enrichment, we have identified 28 metabolites that showed statistically significant changes between pallid and wild-type control. These metabolites included amino acids, nucleobase-containing compounds and lysophospholipids. Interestingly, pallid mice displayed increased hippocampal levels of the neurotransmitters glutamate and N-acetyl-aspartyl-glutamic acid (NAAG) and their precursor glutamine. Expression of the sodium-coupled neutral amino acid transporter 1 (SNAT1), which transports glutamine into neurons, was also upregulated. Conversely, levels of the neurotransmitter precursors phenylalanine and tryptophan were decreased. Interestingly, many of these changes could be mapped to overlapping metabolic pathways. The observed metabolic alterations are likely to affect neurotransmission and neuronal homeostasis and in turn could mediate the memory and behavioural impairments observed in BLOC-1-deficient mice.S. M. van LiempdD. CabreraF. Y. LeeE. GonzálezE. C. Dell’AngelicaC. A. GhianiJ. M. Falcon-PerezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. M. van Liempd D. Cabrera F. Y. Lee E. González E. C. Dell’Angelica C. A. Ghiani J. M. Falcon-Perez BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
description	Abstract Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by BLOC-1 deficiency in pallid mice, which carry a null mutation in the Bloc1s6 gene encoding an essential component of this complex. The metabolome of the hippocampus of pallid mice was analysed using an untargeted, liquid chromatography-coupled mass spectrometric approach. After data pre-treatment, statistical analysis and pathway enrichment, we have identified 28 metabolites that showed statistically significant changes between pallid and wild-type control. These metabolites included amino acids, nucleobase-containing compounds and lysophospholipids. Interestingly, pallid mice displayed increased hippocampal levels of the neurotransmitters glutamate and N-acetyl-aspartyl-glutamic acid (NAAG) and their precursor glutamine. Expression of the sodium-coupled neutral amino acid transporter 1 (SNAT1), which transports glutamine into neurons, was also upregulated. Conversely, levels of the neurotransmitter precursors phenylalanine and tryptophan were decreased. Interestingly, many of these changes could be mapped to overlapping metabolic pathways. The observed metabolic alterations are likely to affect neurotransmission and neuronal homeostasis and in turn could mediate the memory and behavioural impairments observed in BLOC-1-deficient mice.
format	article
author	S. M. van Liempd D. Cabrera F. Y. Lee E. González E. C. Dell’Angelica C. A. Ghiani J. M. Falcon-Perez
author_facet	S. M. van Liempd D. Cabrera F. Y. Lee E. González E. C. Dell’Angelica C. A. Ghiani J. M. Falcon-Perez
author_sort	S. M. van Liempd
title	BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
title_short	BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
title_full	BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
title_fullStr	BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
title_full_unstemmed	BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
title_sort	bloc-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b75ff7c17f24ce9892424db41d9bd69
work_keys_str_mv	AT smvanliempd bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT dcabrera bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT fylee bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT egonzalez bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT ecdellangelica bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT caghiani bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus AT jmfalconperez bloc1deficiencycausesalterationsinaminoacidprofileandinphospholipidandadenosinemetabolisminthepostnatalmousehippocampus
_version_	1718384770085289984

BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus

Ejemplares similares