Src Activates Retrograde Membrane Traffic Through Phosphorylation of GBF1

Overview

Journal Elife

Specialty Biology

Date 2021 Dec 6

PMID 34870592

Citations 8

Authors

Joanne Chia

Shyi-Chyi Wang

Sheena Wee

David James Gill

Felicia Tay

Srinivasaraghavan Kannan

Chandra S Verma

Jayantha Gunaratne

Frederic A Bard

Affiliations

Soon will be listed here.

Abstract

The Src tyrosine kinase controls cancer-critical protein glycosylation through Golgi to ER relocation of GALNTs enzymes. How Src induces this trafficking event is unknown. Golgi to ER transport depends on the GTP exchange factor (GEF) GBF1 and small GTPase Arf1. Here, we show that Src induces the formation of tubular transport carriers containing GALNTs. The kinase phosphorylates GBF1 on 10 tyrosine residues; two of them, Y876 and Y898, are located near the C-terminus of the Sec7 GEF domain. Their phosphorylation promotes GBF1 binding to the GTPase; molecular modeling suggests partial melting of the Sec7 domain and intramolecular rearrangement. GBF1 mutants defective for these rearrangements prevent binding, carrier formation, and GALNTs relocation, while phosphomimetic GBF1 mutants induce tubules. In sum, Src promotes GALNTs relocation by promoting GBF1 binding to Arf1. Based on residue conservation, similar regulation of GEF-Arf complexes by tyrosine phosphorylation could be a conserved and widespread mechanism.

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References

Qiao Y, Molina H, Pandey A, Zhang J, Cole P . Chemical rescue of a mutant enzyme in living cells. Science. 2006; 311(5765):1293-7. DOI: 10.1126/science.1122224. View

Donaldson J, Jackson C . ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol. 2011; 12(6):362-75. PMC: 3245550. DOI: 10.1038/nrm3117. View

Kannan S, Poulsen A, Yang H, Ho M, Ang S, Eldwin T . Probing the binding mechanism of Mnk inhibitors by docking and molecular dynamics simulations. Biochemistry. 2014; 54(1):32-46. DOI: 10.1021/bi501261j. View

Gommel D, Memon A, Heiss A, Lottspeich F, Pfannstiel J, Lechner J . Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23. EMBO J. 2001; 20(23):6751-60. PMC: 125325. DOI: 10.1093/emboj/20.23.6751. View

Nguyen A, Chia J, Ros M, Hui K, Saltel F, Bard F . Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis. Cancer Cell. 2017; 32(5):639-653.e6. DOI: 10.1016/j.ccell.2017.10.001. View

Ros M, Nguyen A, Chia J, Le Tran S, Le Guezennec X, McDowall R . ER-resident oxidoreductases are glycosylated and trafficked to the cell surface to promote matrix degradation by tumour cells. Nat Cell Biol. 2020; 22(11):1371-1381. DOI: 10.1038/s41556-020-00590-w. View

Meissner J, Bhatt J, Lee E, Styers M, Ivanova A, Kahn R . The ARF guanine nucleotide exchange factor GBF1 is targeted to Golgi membranes through a PIP-binding domain. J Cell Sci. 2018; 131(3). PMC: 5826047. DOI: 10.1242/jcs.210245. View

Bard F, Chia J . Cracking the Glycome Encoder: Signaling, Trafficking, and Glycosylation. Trends Cell Biol. 2016; 26(5):379-388. DOI: 10.1016/j.tcb.2015.12.004. View

Jian X, Cavenagh M, Gruschus J, Randazzo P, Kahn R . Modifications to the C-terminus of Arf1 alter cell functions and protein interactions. Traffic. 2010; 11(6):732-42. PMC: 2874613. DOI: 10.1111/j.1600-0854.2010.01054.x. View

10.

Krauss M, Jia J, Roux A, Beck R, Wieland F, De Camilli P . Arf1-GTP-induced tubule formation suggests a function of Arf family proteins in curvature acquisition at sites of vesicle budding. J Biol Chem. 2008; 283(41):27717-27723. PMC: 3762545. DOI: 10.1074/jbc.M804528200. View

11.

Shomron O, Nevo-Yassaf I, Aviad T, Yaffe Y, Zahavi E, Dukhovny A . COPII collar defines the boundary between ER and ER exit site and does not coat cargo containers. J Cell Biol. 2021; 220(6). PMC: 8054201. DOI: 10.1083/jcb.201907224. View

12.

Itzhak D, Tyanova S, Cox J, Borner G . Global, quantitative and dynamic mapping of protein subcellular localization. Elife. 2016; 5. PMC: 4959882. DOI: 10.7554/eLife.16950. View

13.

Giannotta M, Ruggiero C, Grossi M, Cancino J, Capitani M, Pulvirenti T . The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. EMBO J. 2012; 31(13):2869-81. PMC: 3395092. DOI: 10.1038/emboj.2012.134. View

14.

Thomas S, Brugge J . Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol. 1997; 13:513-609. DOI: 10.1146/annurev.cellbio.13.1.513. View

15.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

16.

DellAngelica E, Puertollano R, Mullins C, Aguilar R, Vargas J, Hartnell L . GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex. J Cell Biol. 2000; 149(1):81-94. PMC: 2175099. DOI: 10.1083/jcb.149.1.81. View

17.

Sali A, Blundell T . Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993; 234(3):779-815. DOI: 10.1006/jmbi.1993.1626. View

18.

Kawamoto K, Yoshida Y, Tamaki H, Torii S, Shinotsuka C, Yamashina S . GBF1, a guanine nucleotide exchange factor for ADP-ribosylation factors, is localized to the cis-Golgi and involved in membrane association of the COPI coat. Traffic. 2002; 3(7):483-95. DOI: 10.1034/j.1600-0854.2002.30705.x. View

19.

Zhao X, Lasell T, Melancon P . Localization of large ADP-ribosylation factor-guanine nucleotide exchange factors to different Golgi compartments: evidence for distinct functions in protein traffic. Mol Biol Cell. 2002; 13(1):119-33. PMC: 65077. DOI: 10.1091/mbc.01-08-0420. View

20.

Cox R, Mason-Gamer R, Jackson C, Segev N . Phylogenetic analysis of Sec7-domain-containing Arf nucleotide exchangers. Mol Biol Cell. 2004; 15(4):1487-505. PMC: 379250. DOI: 10.1091/mbc.e03-06-0443. View