Sulfatase modifying factor 1 trafficking through the cells: From endoplasmic reticulum to the endoplasmic reticulum

Ester Zito, Mario Buono, Stefano Pepe, Carmine Settembre, Ida Annunziata, Enrico Maria Surace, Thomas Dierks, Maria Monti, Marianna Cozzolino, Piero Pucci, Andrea Ballabio, Maria Pia Cosma

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2443-2453
Number of pages11
JournalEMBO Journal
Volume26
Issue number10
DOIs
Publication statusPublished - May 16 2007

Keywords

  • Endoplasmic reticulum
  • Protein secretion and uptake
  • Sulfatases
  • SUMF1
  • Trafficking

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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  • Cite this

    Zito, E., Buono, M., Pepe, S., Settembre, C., Annunziata, I., Surace, E. M., Dierks, T., Monti, M., Cozzolino, M., Pucci, P., Ballabio, A., & Cosma, M. P. (2007). Sulfatase modifying factor 1 trafficking through the cells: From endoplasmic reticulum to the endoplasmic reticulum. EMBO Journal, 26(10), 2443-2453. https://doi.org/10.1038/sj.emboj.7601695