title: 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.
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Ilka
authors: I
authors: Wilhelmi
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Regina
authors: R
authors: Kanski
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Alexander
authors: A
authors: Neumann
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Olga
authors: O
authors: Herdt
authors: Department of Cell Biology and Cell Pathology, Philipps-University Marburg, Robert Koch Strae 6, 35037 Marburg, Germany.
authors: Florian
authors: F
authors: Hoff
authors: Department of Cell Biology and Cell Pathology, Philipps-University Marburg, Robert Koch Strae 6, 35037 Marburg, Germany.
authors: Ralf
authors: R
authors: Jacob
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Marco
authors: M
authors: Preußner
authors: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
authors: Florian
authors: F
authors: Heyd
mesh_terms: D017398:Alternative Splicing; D001692:Biological Transport; D022181:COP-Coated Vesicles / Q000378:metabolism*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005091:Exons; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020033:Protein Isoforms; D021381:Protein Transport; D013601:T-Lymphocytes / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C517555:SEC16A protein, human; D033921:Vesicular Transport Proteins