The TRAPP complex mediates secretion arrest induced by stress granule assembly.


Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
01 10 2019
Historique:
received: 04 02 2019
revised: 31 07 2019
accepted: 01 08 2019
pubmed: 21 8 2019
medline: 31 12 2019
entrez: 21 8 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31429971
doi: 10.15252/embj.2019101704
pmc: PMC6769382
doi:

Substances chimiques

Membrane Transport Proteins 0
CDC2 Protein Kinase EC 2.7.11.22
Cyclin-Dependent Kinase 2 EC 2.7.11.22

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e101704

Subventions

Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : 670881
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : IG2013_14761
Pays : International
Organisme : Telethon
ID : TGM11CB1
Pays : Italy

Informations de copyright

© 2019 The Authors.

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Auteurs

Francesca Zappa (F)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Cathal Wilson (C)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Giuseppe Di Tullio (G)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Michele Santoro (M)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Piero Pucci (P)

Federico II University, Naples, Italy.

Maria Monti (M)

Federico II University, Naples, Italy.

Davide D'Amico (D)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Sandra Pisonero-Vaquero (S)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Rossella De Cegli (R)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Alessia Romano (A)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Moin A Saleem (MA)

Bristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.

Elena Polishchuk (E)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Mario Failli (M)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Laura Giaquinto (L)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.

Maria Antonietta De Matteis (MA)

Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy.
Federico II University, Naples, Italy.

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