Ca(2+) import into the lumen of the trans-Golgi network (TGN) by the secretory pathway calcium ATPase1 (SPCA1) is required for the sorting of secretory cargo. How is Ca(2+) retained in the lumen of the Golgi, and what is its role in cargo sorting? We show here that a soluble, lumenal Golgi resident protein, Cab45, is required for SPCA1-dependent Ca(2+) import into the TGN; it binds secretory cargo in a Ca(2+)-dependent reaction and is required for its sorting at the TGN.

V. Malhotra is an Institució Catalana de Recerca i Estudis Avançats (ICREA) professor at the Center for Genomic Regulation, and the work in his laboratory is funded by grants from Plan Nacional (BFU2008-00414), Consolider (CSD2009-00016), Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) Grups de Recerca Emergents (SGR2009-1488; AGAUR-Catalan Government), and the European Research Council (268692). The group of J. von Blume is funded by an Emmy Noether fellowship (project BL 1186/1-1) of the Deutsche Forschungsgemeinschaft (DFG). M.A. Valverde is the recipient of an ICREA Academia Award and the work in his laboratory is supported by the Spanish ministry of Science and Innovation (SAF2012-38140), Fondo de Investigación Sanitaria (RD12/0042/0014), FEDER Funds, and Generalitat de Catalunya (SGR05-266)