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SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes

SIDT2 is a lysosomal protein involved in the degradation of nucleic acids and the transport of cholesterol between membranes. Previous studies identified two “cholesterol recognition/interaction amino acid consensus” (CRAC) motifs in SIDT1 and SIDT2 members. We have previously shown that the first C...

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Detalles Bibliográficos
Autores principales: Sampieri, Alicia, Asanov, Alexander, Méndez-Acevedo, Kevin Manuel, Vaca, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571540/
https://www.ncbi.nlm.nih.gov/pubmed/37830567
http://dx.doi.org/10.3390/cells12192353
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author Sampieri, Alicia
Asanov, Alexander
Méndez-Acevedo, Kevin Manuel
Vaca, Luis
author_facet Sampieri, Alicia
Asanov, Alexander
Méndez-Acevedo, Kevin Manuel
Vaca, Luis
author_sort Sampieri, Alicia
collection PubMed
description SIDT2 is a lysosomal protein involved in the degradation of nucleic acids and the transport of cholesterol between membranes. Previous studies identified two “cholesterol recognition/interaction amino acid consensus” (CRAC) motifs in SIDT1 and SIDT2 members. We have previously shown that the first CRAC motif (CRAC-1) is essential for protein translocation to the PM upon cholesterol depletion in the cell. In the present study, we show that SIDT2 and the apolipoprotein A1 (ApoA1) form a complex which requires the second CRAC-2 motif in SIDT2 to be established. The overexpression of SIDT2 and ApoA1 results in enhanced ApoA1 secretion by HepG2 cells. This is not observed when overexpressing the SIDT2 with the CRAC-2 domain mutated to render it unfunctional. All these results provide evidence of a novel role for SIDT2 as a protein forming a complex with ApoA1 and enhancing its secretion to the extracellular space.
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spelling pubmed-105715402023-10-14 SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes Sampieri, Alicia Asanov, Alexander Méndez-Acevedo, Kevin Manuel Vaca, Luis Cells Article SIDT2 is a lysosomal protein involved in the degradation of nucleic acids and the transport of cholesterol between membranes. Previous studies identified two “cholesterol recognition/interaction amino acid consensus” (CRAC) motifs in SIDT1 and SIDT2 members. We have previously shown that the first CRAC motif (CRAC-1) is essential for protein translocation to the PM upon cholesterol depletion in the cell. In the present study, we show that SIDT2 and the apolipoprotein A1 (ApoA1) form a complex which requires the second CRAC-2 motif in SIDT2 to be established. The overexpression of SIDT2 and ApoA1 results in enhanced ApoA1 secretion by HepG2 cells. This is not observed when overexpressing the SIDT2 with the CRAC-2 domain mutated to render it unfunctional. All these results provide evidence of a novel role for SIDT2 as a protein forming a complex with ApoA1 and enhancing its secretion to the extracellular space. MDPI 2023-09-26 /pmc/articles/PMC10571540/ /pubmed/37830567 http://dx.doi.org/10.3390/cells12192353 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sampieri, Alicia
Asanov, Alexander
Méndez-Acevedo, Kevin Manuel
Vaca, Luis
SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title_full SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title_fullStr SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title_full_unstemmed SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title_short SIDT2 Associates with Apolipoprotein A1 (ApoA1) and Facilitates ApoA1 Secretion in Hepatocytes
title_sort sidt2 associates with apolipoprotein a1 (apoa1) and facilitates apoa1 secretion in hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571540/
https://www.ncbi.nlm.nih.gov/pubmed/37830567
http://dx.doi.org/10.3390/cells12192353
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