Secretory cargo sorting by Ca2+-dependent Cab45 oligomerization at the trans-Golgi network
| Autor: | Bianca Habermann, Alvaro H. Crevenna, Julia von Blume, Andreas Maiser, Gisela Beck, Jens Prescher, Don C. Lamb, Christine Kienzle, Kira Bartnik, Derya Emin, Heinrich Leonhardt, Mehrshad Pakdel, Birgit Blank |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine cells macromolecular substances Biology environment and public health 03 medical and health sciences symbols.namesake Report Extracellular Humans Calcium Signaling Research Articles Actin Secretory pathway Glycoproteins Calcium signaling Secretory Pathway Calcium-Binding Proteins Proteins Biological Transport Cell Biology Golgi apparatus In vitro Transmembrane protein Cell biology carbohydrates (lipids) 030104 developmental biology Secretory protein symbols Calcium HeLa Cells trans-Golgi Network |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201601089 |
| Popis: | Crevenna et al. examine the mechanism by which secretory cargoes are segregated at the trans-Golgi network (TGN) for release into the extracellular space. The authors demonstrate that Ca2+-dependent changes in Cab45 oligomerization mediate sorting of specific cargo molecules at the TGN. 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 Ca2+, 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 Ca2+. These Cab45 oligomers specifically bind secretory proteins, such as COMP and LyzC, in a Ca2+-dependent manner in vitro. In intact cells, mutation of the Ca2+-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 Ca2+ pump (SPCA1) in specific TGN microdomains. These findings reveal that Ca2+-dependent changes in Cab45 mediate sorting of specific cargo molecules at the TGN. |
| Databáze: | OpenAIRE |
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