Sec16 alternative splicing dynamically controls COPII transport efficiency

作者：Wilhelmi Ilka; Kanski Regina; Neumann Alexander; Herdt Olga; Hoff Florian; Jacob Ralf; Preussner Marco; Heyd Florian^*

来源：Nature Communications, 2016, 7(1): 12347.

DOI：10.1038/ncomms12347

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.

• 出版日期2016-8