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J Cell Biol. 2016 May 9;213(3):305-14. doi: 10.1083/jcb.201601089. Epub 2016 May 2.

Secretory cargo sorting by Ca2+-dependent Cab45 oligomerization at the trans-Golgi network.

Author information

1
Physical Chemistry, Department of Chemistry Center for Nanoscience, Nanosystems Initiative Munich and Center for Integrated Protein Science Munich, Ludwig Maximilians University Munich, 81377 Munich, Germany vonblume@biochem.mpg.de alvaro.crevenna@cup.uni-muenchen.de.
2
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
3
Department of Biology II, Ludwig Maximilian University Munich, 82152 Martinsried, Germany Center for Integrated Protein Science, Ludwig Maximilians University Munich, 82152 Martinsried, Germany.
4
Physical Chemistry, Department of Chemistry Center for Nanoscience, Nanosystems Initiative Munich and Center for Integrated Protein Science Munich, Ludwig Maximilians University Munich, 81377 Munich, Germany.
5
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany vonblume@biochem.mpg.de alvaro.crevenna@cup.uni-muenchen.de.

Abstract

Sorting and export of transmembrane cargoes and lysosomal hydrolases at the trans-Golgi network (TGN) are well understood. However, elucidation of the mechanism by which secretory cargoes are segregated for their release into the extracellular space remains a challenge. We have previously demonstrated that, in a reaction that requires Ca(2+), the soluble TGN-resident protein Cab45 is necessary for the sorting of secretory cargoes at the TGN. Here, we report that Cab45 reversibly assembles into oligomers in the presence of Ca(2+) These Cab45 oligomers specifically bind secretory proteins, such as COMP and LyzC, in a Ca(2+)-dependent manner in vitro. In intact cells, mutation of the Ca(2+)-binding sites in Cab45 impairs oligomerization, as well as COMP and LyzC sorting. Superresolution microscopy revealed that Cab45 colocalizes with secretory proteins and the TGN Ca(2+) pump (SPCA1) in specific TGN microdomains. These findings reveal that Ca(2+)-dependent changes in Cab45 mediate sorting of specific cargo molecules at the TGN.

PMID:
27138253
PMCID:
PMC4862333
DOI:
10.1083/jcb.201601089
[Indexed for MEDLINE]
Free PMC Article

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