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

Crevenna, Alvaro H.; Blank, Birgit; Maiser, Andreas; Emin, Derya; Prescher, Jens; Beck, Gisela; Kienzle, Christine; Bartnik, Kira; Habermann, Bianca; Pakdel, Mehrshad; Leonhardt, Heinrich; Lamb, Don C. and Blume, Julia von (2016): Secretory cargo sorting by Ca2+-dependent Cab45 oligomerization at the trans-Golgi network. In: Journal of Cell Biology, Vol. 213, No. 3: pp. 305-314

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 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 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 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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry; Biology > Department Biology II
• Subjects: 500 Science > 540 Chemistry; 500 Science > 570 Life sciences; biology
• ISSN: 0021-9525
• Language: English