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Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders
Stefano Sechi1, Angela Karimpour-Ghahnavieh1, Anna Frappaolo1
1Istituto di Biologia e Patologia Molecolari del CNR, c/o Dipartimento di Biologia e Biotecnologie, Sapienza Università di Roma, Piazzale A. Moro 5, 00185 Roma, Italy.
Abstract:
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.
Insights
Golgi phosphoprotein 3 (GOLPH3) interacts with proteins regulating cell division and trafficking. This study identifies GOLPH3
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Golgi phosphoprotein 3 (GOLPH3) is a conserved protein at the Golgi apparatus.
- GOLPH3 influences Golgi structure and vesicle transport, dependent on phosphatidylinositol 4-phosphate (PI(4)P).
- GOLPH3 overexpression correlates with poor cancer prognosis, but its role in malignancy is unclear.
Purpose of the Study:
- To identify the protein-protein interaction network (interactome) of Drosophila GOLPH3.
- To elucidate molecular mechanisms linking GOLPH3 to cancer and other diseases.
Main Methods:
- Affinity purification coupled with mass spectrometry (AP-MS) was used to identify GOLPH3 interactors in Drosophila testes.
- Bioinformatic analysis was performed on the identified protein-protein interaction network.
Main Results:
- The GOLPH3 interactome is enriched for proteins involved in vesicle trafficking, cell proliferation, and cytoskeleton dynamics.
- Drosophila GOLPH3 (dGOLPH3) interacts with orthologs of Fragile X mental retardation protein and Ataxin-2.
- These interactions suggest a role for GOLPH3 in the nervous system.
Conclusions:
- GOLPH3's interactome provides novel insights into its function in membrane trafficking and cell division.
- GOLPH3 may play a role in the pathophysiology of neurological disorders.
- Identified GOLPH3-associated targets could be relevant for cancer and other disease therapies.
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