Pular para o conteúdo
Merck

Sec16 alternative splicing dynamically controls COPII transport efficiency.

Nature communications (2016-08-06)
Ilka Wilhelmi, Regina Kanski, Alexander Neumann, Olga Herdt, Florian Hoff, Ralf Jacob, Marco Preußner, Florian Heyd
RESUMO

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.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Anti-ERGIC-53/p58 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-SAR1A antibody produced in mouse, clone 3G5, purified immunoglobulin, buffered aqueous solution