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Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders

Golgi phosphoprotein 3 (GOLPH3) is a highly conserved peripheral membrane protein localized to the Golgi apparatus and the cytosol. GOLPH3 binding to Golgi membranes depends on phosphatidylinositol 4-phosphate [PI(4)P] and regulates Golgi architecture and vesicle trafficking. GOLPH3 overexpression h...

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Autores principales: Sechi, Stefano, Karimpour-Ghahnavieh, Angela, Frappaolo, Anna, Di Francesco, Laura, Piergentili, Roberto, Schininà, Eugenia, D’Avino, Pier Paolo, Giansanti, Maria Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468827/
https://www.ncbi.nlm.nih.gov/pubmed/34571985
http://dx.doi.org/10.3390/cells10092336
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author Sechi, Stefano
Karimpour-Ghahnavieh, Angela
Frappaolo, Anna
Di Francesco, Laura
Piergentili, Roberto
Schininà, Eugenia
D’Avino, Pier Paolo
Giansanti, Maria Grazia
author_facet Sechi, Stefano
Karimpour-Ghahnavieh, Angela
Frappaolo, Anna
Di Francesco, Laura
Piergentili, Roberto
Schininà, Eugenia
D’Avino, Pier Paolo
Giansanti, Maria Grazia
author_sort Sechi, Stefano
collection PubMed
description Golgi phosphoprotein 3 (GOLPH3) is a highly conserved peripheral membrane protein localized to the Golgi apparatus and the cytosol. GOLPH3 binding to Golgi membranes depends on phosphatidylinositol 4-phosphate [PI(4)P] and regulates Golgi architecture and vesicle trafficking. GOLPH3 overexpression has been correlated with poor prognosis in several cancers, but the molecular mechanisms that link GOLPH3 to malignant transformation are poorly understood. We recently showed that PI(4)P-GOLPH3 couples membrane trafficking with contractile ring assembly during cytokinesis in dividing Drosophila spermatocytes. Here, we use affinity purification coupled with mass spectrometry (AP-MS) to identify the protein-protein interaction network (interactome) of Drosophila GOLPH3 in testes. Analysis of the GOLPH3 interactome revealed enrichment for proteins involved in vesicle-mediated trafficking, cell proliferation and cytoskeleton dynamics. In particular, we found that dGOLPH3 interacts with the Drosophila orthologs of Fragile X mental retardation protein and Ataxin-2, suggesting a potential role in the pathophysiology of disorders of the nervous system. Our findings suggest novel molecular targets associated with GOLPH3 that might be relevant for therapeutic intervention in cancers and other human diseases.
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spelling pubmed-84688272021-09-27 Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders Sechi, Stefano Karimpour-Ghahnavieh, Angela Frappaolo, Anna Di Francesco, Laura Piergentili, Roberto Schininà, Eugenia D’Avino, Pier Paolo Giansanti, Maria Grazia Cells Article Golgi phosphoprotein 3 (GOLPH3) is a highly conserved peripheral membrane protein localized to the Golgi apparatus and the cytosol. GOLPH3 binding to Golgi membranes depends on phosphatidylinositol 4-phosphate [PI(4)P] and regulates Golgi architecture and vesicle trafficking. GOLPH3 overexpression has been correlated with poor prognosis in several cancers, but the molecular mechanisms that link GOLPH3 to malignant transformation are poorly understood. We recently showed that PI(4)P-GOLPH3 couples membrane trafficking with contractile ring assembly during cytokinesis in dividing Drosophila spermatocytes. Here, we use affinity purification coupled with mass spectrometry (AP-MS) to identify the protein-protein interaction network (interactome) of Drosophila GOLPH3 in testes. Analysis of the GOLPH3 interactome revealed enrichment for proteins involved in vesicle-mediated trafficking, cell proliferation and cytoskeleton dynamics. In particular, we found that dGOLPH3 interacts with the Drosophila orthologs of Fragile X mental retardation protein and Ataxin-2, suggesting a potential role in the pathophysiology of disorders of the nervous system. Our findings suggest novel molecular targets associated with GOLPH3 that might be relevant for therapeutic intervention in cancers and other human diseases. MDPI 2021-09-06 /pmc/articles/PMC8468827/ /pubmed/34571985 http://dx.doi.org/10.3390/cells10092336 Text en © 2021 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
Sechi, Stefano
Karimpour-Ghahnavieh, Angela
Frappaolo, Anna
Di Francesco, Laura
Piergentili, Roberto
Schininà, Eugenia
D’Avino, Pier Paolo
Giansanti, Maria Grazia
Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title_full Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title_fullStr Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title_full_unstemmed Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title_short Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
title_sort identification of golph3 partners in drosophila unveils potential novel roles in tumorigenesis and neural disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468827/
https://www.ncbi.nlm.nih.gov/pubmed/34571985
http://dx.doi.org/10.3390/cells10092336
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