Monday, 02 May, 2016

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

A. H. Crevenna, B. Blank, A. Maiser, D. Emin, J. Prescher, G. Beck, C. Kienzle, K. Bartnik, B. Habermann, M. Pakdel, H. Leonhardt, D. C. Lamb and J. von Blume -
Journal of Cell Biology, 10.1083/jcb.201601089 (2016)

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.

Article on journal´s webpage