| Structural highlights
Function
GOLP3_HUMAN Mediates the cis and medial Golgi localization of mannosyltransferases through direct binding of their cytosolic domains. Involved in modulation of mTOR signaling. Involved in the regulation of mitochondrial lipids, leading to increase of mitochondrial mass. Potential oncogene.[1] [2] [3]
Publication Abstract from PubMed
The multiple cisternae of the Golgi apparatus contain resident membrane proteins crucial for lipid and protein glycosylation. How Golgi residents remain in their designated compartments despite a constant flow of secretory cargo is incompletely understood. Here, we determine the structure of the COPI vesicle coat containing GOLPH3, an adaptor protein that binds the cytosolic tails of many Golgi residents. Analysis of this structure, together with structure-guided mutagenesis and functional assays, reveals how GOLPH3 uses coincidence detection of COPI and lipids to engage Golgi residents preferentially at late cisternae. Our findings rationalize the logic of cisternal maturation and explain how COPI can engage different types of substrates in different Golgi cisternae to retrieve some proteins back to the ER while retaining others within the Golgi apparatus.
The mechanistic basis of cargo selection during Golgi maturation.,Taylor RJ, Zubkov N, Ciazynska KA, Kaufman JGG, Tagiltsev G, Owen DJ, Briggs JAG, Munro S Sci Adv. 2025 Oct 3;11(40):eaea0016. doi: 10.1126/sciadv.aea0016. Epub 2025 Oct , 3. PMID:41042862[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nakashima-Kamimura N, Asoh S, Ishibashi Y, Mukai Y, Shidara Y, Oda H, Munakata K, Goto Y, Ohta S. MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction. J Cell Sci. 2005 Nov 15;118(Pt 22):5357-67. Epub 2005 Nov 1. PMID:16263763 doi:http://dx.doi.org/10.1242/jcs.02645
- ↑ Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao Y, Rimm DL, Protopopov A, Wong KK, Chin L. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature. 2009 Jun 25;459(7250):1085-90. doi: 10.1038/nature08109. PMID:19553991 doi:http://dx.doi.org/10.1038/nature08109
- ↑ Wood CS, Schmitz KR, Bessman NJ, Setty TG, Ferguson KM, Burd CG. PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol. 2009 Dec 28;187(7):967-75. Epub 2009 Dec 21. PMID:20026658 doi:10.1083/jcb.200909063
- ↑ Taylor RJ, Zubkov N, Ciazynska KA, Kaufman JGG, Tagiltsev G, Owen DJ, Briggs JAG, Munro S. The mechanistic basis of cargo selection during Golgi maturation. Sci Adv. 2025 Oct 3;11(40):eaea0016. PMID:41042862 doi:10.1126/sciadv.aea0016
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