RESUMO
Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.
Assuntos
Neoplasias da Mama/enzimologia , Matriz Extracelular/enzimologia , Complexo de Golgi/enzimologia , Macrófagos/enzimologia , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Nucleobindinas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Cálcio/metabolismo , Sinalização do Cálcio , Movimento Celular , Matriz Extracelular/patologia , Feminino , Gelatina/metabolismo , Células HEK293 , Células HeLa , Humanos , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Nucleobindinas/genética , Transporte Proteico , Proteólise , Fatores de TempoRESUMO
The TGN is a key compartment for the sorting and secretion of newly synthesized proteins. At the TGN, soluble proteins are sorted based on the instructions carried in their oligosaccharide backbones or by a Ca2+-mediated process that involves the cargo-sorting protein Cab45. Here, we show that Cab45 is phosphorylated by the Golgi-specific protein kinase Fam20C. Mimicking of phosphorylation translocates Cab45 into TGN-derived vesicles, which goes along with an increased export of LyzC, a Cab45 client. Our findings demonstrate that Fam20C plays a key role in the export of Cab45 clients by fine-tuning Cab45 oligomerization and thus impacts Cab45 retention in the TGN.