title: Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic reticulum to the endoplasmic reticulum.
abstract: Sulfatase modifying factor 1 (SUMF1) is the gene mutated in multiple sulfatase deficiency (MSD) that encodes the formylglycine-generating enzyme, an essential activator of all the sulfatases. SUMF1 is a glycosylated enzyme that is resident in the endoplasmic reticulum (ER), although it is also secreted. Here, we demonstrate that upon secretion, SUMF1 can be taken up from the medium by several cell lines. Furthermore, the in vivo engineering of mice liver to produce SUMF1 shows its secretion into the blood serum and its uptake into different tissues. Additionally, we show that non-glycosylated forms of SUMF1 can still be secreted, while only the glycosylated SUMF1 enters cells, via a receptor-mediated mechanism. Surprisingly, following its uptake, SUMF1 shuttles from the plasma membrane to the ER, a route that has to date only been well characterized for some of the toxins. Remarkably, once taken up and relocalized into the ER, SUMF1 is still active, enhancing the sulfatase activities in both cultured cells and mice tissues.
authors: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors: Ester
authors: E
authors: Zito
authors: Mario
authors: M
authors: Buono
authors: Stefano
authors: S
authors: Pepe
authors: Carmine
authors: C
authors: Settembre
authors: Ida
authors: I
authors: Annunziata
authors: Enrico Maria
authors: EM
authors: Surace
authors: Thomas
authors: T
authors: Dierks
authors: Maria
authors: M
authors: Monti
authors: Marianna
authors: M
authors: Cozzolino
authors: Piero
authors: P
authors: Pucci
authors: Andrea
authors: A
authors: Ballabio
authors: Maria Pia
authors: MP
authors: Cosma
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D050862:Oxidoreductases Acting on Sulfur Group Donors; D021381:Protein Transport / Q000502:physiology*; D013429:Sulfatases / Q000032:analysis / Q000378:metabolism*
chemical_list: D050862:Oxidoreductases Acting on Sulfur Group Donors; C519507:Sumf1 protein, mouse; C480483:SUMF1 protein, human; D013429:Sulfatases