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Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic reticulum to the endoplasmic reticulum
Author(s) -
Zito Ester,
Buono Mario,
Pepe Stefano,
Settembre Carmine,
Annunziata Ida,
Surace Enrico Maria,
Dierks Thomas,
Monti Maria,
Cozzolino Marianna,
Pucci Piero,
Ballabio Andrea,
Cosma Maria Pia
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601695
Subject(s) - endoplasmic reticulum , library science , biology , genetics , computer science
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.