Identification of protein interactors with fly GOLPH3 points to potential targets for cancer and other therapeutics

Cells. 2021 Sep 6;10(9):2336. doi: 10.3390/cells10092336.

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

Sechi S, Karimpour-Ghahnavieh A, Frappaolo A, Di Francesco L, Piergentili R, Schininà E, D'Avino PP, Giansanti MG

Author information:
(1)Istituto 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.
(2)Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Sapienza Università di
Roma, Piazzale A. Moro 5, 00185 Roma, Italy.
(3)Department of Pathology, University of Cambridge, Tennis Court Road,
Cambridge CB2 1QP, UK.

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."

DOI: 10.3390/cells10092336
PMID: 34571985