The TRAPP Complex Mediates Secretion Arrest Induced by Stress Granule Assembly

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2019 Aug 21

PMID 31429971

Citations 13

Authors

Francesca Zappa

Cathal Wilson

Giuseppe Di Tullio

Michele Santoro

Piero Pucci

Maria Monti

Davide DAmico

Sandra Pisonero-Vaquero

Rossella De Cegli

Alessia Romano

Moin A Saleem

Elena Polishchuk

Mario Failli

Laura Giaquinto

Maria Antonietta De Matteis

Affiliations

Soon will be listed here.

Abstract

The TRAnsport Protein Particle (TRAPP) complex controls multiple membrane trafficking steps and is strategically positioned to mediate cell adaptation to diverse environmental conditions, including acute stress. We have identified the TRAPP complex as a component of a branch of the integrated stress response that impinges on the early secretory pathway. The TRAPP complex associates with and drives the recruitment of the COPII coat to stress granules (SGs) leading to vesiculation of the Golgi complex and arrest of ER export. The relocation of the TRAPP complex and COPII to SGs only occurs in cycling cells and is CDK1/2-dependent, being driven by the interaction of TRAPP with hnRNPK, a CDK substrate that associates with SGs when phosphorylated. In addition, CDK1/2 inhibition impairs TRAPP complex/COPII relocation to SGs while stabilizing them at ER exit sites. Importantly, the TRAPP complex controls the maturation of SGs. SGs that assemble in TRAPP-depleted cells are smaller and are no longer able to recruit RACK1 and Raptor, two TRAPP-interactive signaling proteins, sensitizing cells to stress-induced apoptosis.

Citing Articles

TDP43 aggregation at ER-exit sites impairs ER-to-Golgi transport.

Wu H, Wang L, Sow B, Leow D, Zhu J, Gallo K Nat Commun. 2024; 15(1):9026.

PMID: 39424779 PMC: 11489672. DOI: 10.1038/s41467-024-52706-7.

A Humanized Yeast Model for Studying TRAPP Complex Mutations; Proof-of-Concept Using Variants from an Individual with a -Associated Neurodevelopmental Syndrome.

Zykaj E, Abboud C, Asadi P, Warsame S, Almousa H, Milev M Cells. 2024; 13(17.

PMID: 39273027 PMC: 11394476. DOI: 10.3390/cells13171457.

Signaling plasticity in the integrated stress response.

Boone M, Zappa F Front Cell Dev Biol. 2023; 11:1271141.

PMID: 38143923 PMC: 10740175. DOI: 10.3389/fcell.2023.1271141.

Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle.

Hu S, Zhang Y, Yi Q, Yang C, Liu Y, Bai Y Nat Commun. 2023; 14(1):7782.

PMID: 38012130 PMC: 10682001. DOI: 10.1038/s41467-023-43470-1.

Stress granules and hormetic adaptation of cancer.

Redding A, Grabocka E Trends Cancer. 2023; 9(12):995-1005.

PMID: 37704502 PMC: 10843007. DOI: 10.1016/j.trecan.2023.08.005.

References

Ballock R, OKeefe R . The biology of the growth plate. J Bone Joint Surg Am. 2003; 85(4):715-26. View

Choi M, Chan C, Chan D, Luk K, Cheah K, Tanner J . Biochemical consequences of sedlin mutations that cause spondyloepiphyseal dysplasia tarda. Biochem J. 2009; 423(2):233-42. DOI: 10.1042/BJ20090541. View

Takahashi M, Higuchi M, Matsuki H, Yoshita M, Ohsawa T, Oie M . Stress granules inhibit apoptosis by reducing reactive oxygen species production. Mol Cell Biol. 2012; 33(4):815-29. PMC: 3571346. DOI: 10.1128/MCB.00763-12. View

Henrotin Y, Bruckner P, Pujol J . The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis Cartilage. 2003; 11(10):747-55. DOI: 10.1016/s1063-4584(03)00150-x. View

Shevchenko A, Tomas H, Havlis J, Olsen J, Mann M . In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2007; 1(6):2856-60. DOI: 10.1038/nprot.2006.468. View

Lord C, Bhandari D, Menon S, Ghassemian M, Nycz D, Hay J . Sequential interactions with Sec23 control the direction of vesicle traffic. Nature. 2011; 473(7346):181-6. PMC: 3093450. DOI: 10.1038/nature09969. View

Tisdale E, Bourne J, Khosravi-Far R, Der C, Balch W . GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. J Cell Biol. 1992; 119(4):749-61. PMC: 2289685. DOI: 10.1083/jcb.119.4.749. View

Zacharogianni M, Aguilera-Gomez A, Veenendaal T, Smout J, Rabouille C . A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation. Elife. 2014; 3. PMC: 4270098. DOI: 10.7554/eLife.04132. View

Aulas A, Fay M, Szaflarski W, Kedersha N, Anderson P, Ivanov P . Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules. J Vis Exp. 2017; (123). PMC: 5607937. DOI: 10.3791/55656. View

10.

Dubois T, Paleotti O, Mironov A, Fraisier V, Stradal T, De Matteis M . Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics. Nat Cell Biol. 2005; 7(4):353-64. DOI: 10.1038/ncb1244. View

11.

Khattak N, Mir A . Computational analysis of TRAPPC9: candidate gene for autosomal recessive non-syndromic mental retardation. CNS Neurol Disord Drug Targets. 2013; 13(4):699-711. DOI: 10.2174/18715273113129990105. View

12.

Holt L, Tuch B, Villen J, Johnson A, Gygi S, Morgan D . Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution. Science. 2009; 325(5948):1682-6. PMC: 2813701. DOI: 10.1126/science.1172867. View

13.

David A, Dolan B, Hickman H, Knowlton J, Clavarino G, Pierre P . Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol. 2012; 197(1):45-57. PMC: 3317795. DOI: 10.1083/jcb.201112145. View

14.

Li C, Luo X, Zhao S, Siu G, Liang Y, Chan H . COPI-TRAPPII activates Rab18 and regulates its lipid droplet association. EMBO J. 2016; 36(4):441-457. PMC: 5694949. DOI: 10.15252/embj.201694866. View

15.

Moujalled D, James J, Yang S, Zhang K, Duncan C, Moujalled D . Phosphorylation of hnRNP K by cyclin-dependent kinase 2 controls cytosolic accumulation of TDP-43. Hum Mol Genet. 2014; 24(6):1655-69. DOI: 10.1093/hmg/ddu578. View

16.

Harripaul R, Vasli N, Mikhailov A, Rafiq M, Mittal K, Windpassinger C . Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families. Mol Psychiatry. 2017; 23(4):973-984. DOI: 10.1038/mp.2017.60. View

17.

De Leo M, Staiano L, Vicinanza M, Luciani A, Carissimo A, Mutarelli M . Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL. Nat Cell Biol. 2016; 18(8):839-850. PMC: 5040511. DOI: 10.1038/ncb3386. View

18.

Jain S, Wheeler J, Walters R, Agrawal A, Barsic A, Parker R . ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell. 2016; 164(3):487-98. PMC: 4733397. DOI: 10.1016/j.cell.2015.12.038. View

19.

Venditti R, Scanu T, Santoro M, Di Tullio G, Spaar A, Gaibisso R . Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. Science. 2012; 337(6102):1668-72. PMC: 3471527. DOI: 10.1126/science.1224947. View

20.

Saurus P, Kuusela S, Dumont V, Lehtonen E, Fogarty C, Lassenius M . Cyclin-dependent kinase 2 protects podocytes from apoptosis. Sci Rep. 2016; 6:21664. PMC: 4753499. DOI: 10.1038/srep21664. View