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Sec16 alternative splicing dynamically controls COPII transport efficiency.


ABSTRACT: The transport of secretory proteins from the endoplasmic reticulum (ER) to the Golgi depends on COPII-coated vesicles. While the basic principles of the COPII machinery have been identified, it remains largely unknown how COPII transport is regulated to accommodate tissue- or activation-specific differences in cargo load and identity. Here we show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T-cell activation. Using splice-site blocking morpholinos and CRISPR/Cas9-mediated genome engineering, we show that the number of ER exit sites, COPII dynamics and transport efficiency depend on Sec16 alternative splicing. As the mechanistic basis, we suggest the C-terminal Sec16 domain to be a splicing-controlled protein interaction platform, with individual isoforms showing differential abilities to recruit COPII components. Our work connects the COPII pathway with alternative splicing, adding a new regulatory layer to protein secretion and its adaptation to changing cellular environments.

SUBMITTER: Wilhelmi I 

PROVIDER: S-EPMC4980449 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Sec16 alternative splicing dynamically controls COPII transport efficiency.

Wilhelmi Ilka I   Kanski Regina R   Neumann Alexander A   Herdt Olga O   Hoff Florian F   Jacob Ralf R   Preußner Marco M   Heyd Florian F  

Nature communications 20160805


The transport of secretory proteins from the endoplasmic reticulum (ER) to the Golgi depends on COPII-coated vesicles. While the basic principles of the COPII machinery have been identified, it remains largely unknown how COPII transport is regulated to accommodate tissue- or activation-specific differences in cargo load and identity. Here we show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T-cell activation. Usin  ...[more]

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