Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic reticulum to the endoplasmic reticulum.
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.
Zito
Ester
E
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
Buono
Mario
M
Pepe
Stefano
S
Settembre
Carmine
C
Annunziata
Ida
I
Surace
Enrico Maria
EM
Dierks
Thomas
T
Monti
Maria
M
Cozzolino
Marianna
M
Pucci
Piero
P
Ballabio
Andrea
A
Cosma
Maria Pia
MP
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*
D050862:Oxidoreductases Acting on Sulfur Group Donors; C519507:Sumf1 protein, mouse; C480483:SUMF1 protein, human; D013429:Sulfatases