Actin remodeling by ADF/cofilin is required for cargo sorting at the trans-Golgi network |
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Authors: | Julia von Blume Juan M Duran Elena Forlanelli Anne-Marie Alleaume Mikhail Egorov Roman Polishchuk Henrik Molina Vivek Malhotra |
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Institution: | 1.Department of Cell and Developmental Biology, and 2.Institució Catalana de Recerca i Estudis Avançats, Centre de Regulació Genòmica, 08003 Barcelona, Spain;3.Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (Chieti), Italy |
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Abstract: | Knockdown of the actin-severing protein actin-depolymerizing factor (ADF)/cofilin inhibited export of an exogenously expressed soluble secretory protein from Golgi membranes in Drosophila
melanogaster and mammalian tissue culture cells. A stable isotope labeling by amino acids in cell culture mass spectrometry–based protein profiling revealed that a large number of endogenous secretory proteins in mammalian cells were not secreted upon ADF/cofilin knockdown. Although many secretory proteins were retained, a Golgi-resident protein and a lysosomal hydrolase were aberrantly secreted upon ADF/cofilin knockdown. Overall, our findings indicate that inactivation of ADF/cofilin perturbed the sorting of a subset of both soluble and integral membrane proteins at the trans-Golgi network (TGN). We suggest that ADF/cofilin-dependent actin trimming generates a sorting domain at the TGN, which filters secretory cargo for export, and that uncontrolled growth of this domain causes missorting of proteins. This type of actin-dependent compartmentalization and filtering of secretory cargo at the TGN by ADF/cofilin could explain sorting of proteins that are destined to the cell surface. |
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