title: ADF/cofilin regulates secretory cargo sorting at the TGN via the Ca2+ ATPase SPCA1.
abstract: Actin-severing proteins ADF/cofilin are required for the sorting of secretory cargo at the trans-Golgi network (TGN) in mammalian cells. How do these cytoplasmic proteins interact with the cargoes in the lumen of the TGN? Put simply, how are these two sets of proteins connected across the TGN membrane? Mass spectrometry of cofilin1 immunoprecipitated from HeLa cells revealed the presence of actin and the Ca(2+) ATPase SPCA1. Moreover, cofilin1 was localized to the TGN and bound to SPCA1 via dynamic actin. SPCA1 knockdown, like ADF/cofilin1 knockdown, inhibited Ca(2+) uptake into the TGN and caused missorting of secretory cargo. These defects were rescued by the overexpression of the TGN-localized SPCA1. We propose that ADF/cofilin-dependent severing of actin filaments exposes and promotes the activation of SPCA1, which pumps Ca(2+) into the lumen of the TGN for the sorting of the class of secretory cargo that binds Ca(2+).
authors.affiliation: Department of Cell and Developmental Biology, Centre de Regulacio Genomica, 08003 Barcelona, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: von Blume
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Alleaume
authors.forename: Gerard
authors.initials: G
authors.lastname: Cantero-Recasens
authors.forename: Amy
authors.initials: A
authors.lastname: Curwin
authors.forename: Amado
authors.initials: A
authors.lastname: Carreras-Sureda
authors.forename: Timo
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Josse
authors.initials: J
authors.lastname: van Galen
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakana
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Valverde
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002478:Cells, Cultured; D051345:Destrin / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; C495824:DSTN protein, human; D051345:Destrin; C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium