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bioRxiv · 10.1101/528380

The TRAPP complex mediates secretion arrest induced by stress granule assembly

Zappa, F.·Wilson, C.·Di Tullio, G.·Santoro, M.·Pucci, P.·Monti, M.·D'Amico, D.·Pisonero Vaquero, S.·De Cegli, R.·Romano, A.·Saleem, M.·Polishchuk, E.·Failli, M.·Giaquinto, L.·De Matteis, M. A.
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Abstract

The TRAnsport-Protein-Particle (TRAPP) complex controls multiple membrane trafficking steps and is thus strategically positioned to mediate cell adaptation to diverse environmental conditions, including acute stress. We have identified TRAPP as a key component of a branch of the integrated stress response that impinges on the early secretory pathway. TRAPP associates with and drives the recruitment of the COPII coat to stress granules (SGs) leading to vesiculation of the Golgi complex and an arrest of ER export. Interestingly, the relocation of TRAPP and COPII to SGs only occurs in actively proliferating cells and is CDK1/2-dependent. We show that CDK1/2 activity controls the COPII cycle at ER exit sites (ERES) and that its inhibition prevents TRAPP/COPII relocation to SGs by stabilizing them at the ERES. Importantly, TRAPP is not just a passive constituent of SGs but controls their maturation since SGs that assemble in TRAPP-depleted cells are smaller and are no longer able to recruit RACK1 and Raptor, rendering the cells more prone to undergo apoptosis upon stress exposure.

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Zappa, F., Wilson, C., Di Tullio, G., Santoro, M., Pucci, P., Monti, M., D'Amico, D., Pisonero Vaquero, S., De Cegli, R., Romano, A., Saleem, M., Polishchuk, E., Failli, M., Giaquinto, L., De Matteis, M. A.. 2019-01-23. The TRAPP complex mediates secretion arrest induced by stress granule assembly. https://doi.org/10.1101/528380

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