Our analyses around the basis of antibody recognition as a result of incompatible epitopes just after processing. Additional studies on this situation will need expression of larger amounts of ARSK and/or availability of other ARSKspecific antibodies. ARSK is expressed in all tissues examined within this study and was also identified in eight tissues from rat in M6P glycoproteome analyses (33). Its ubiquitous expression pattern may well suggest a popular and widespread sulfated substrate and indicates that ARSK deficiency in all probability leads to a lysosomal storage disorder, as shown for all other lysosomal sulfatases. Currently, we’re creating an ARSK-deficient mouse model that need to pave the approach to recognize the physiological substrate of this sulfatase and its general pathophysiological relevance. Lastly, the mouse model could allow us to draw conclusions on ARSKdeficient human individuals who so far escaped diagnosis and could possibly be accessible for enzyme replacement therapy. The presence of M6P on ARSK qualifies this sulfatase for such a therapy, which has verified beneficial for treatment of various other lysosomal storage issues.Acknowledgments–We thank Bernhard Schmidt and Olaf Bernhard for mass spectrometry; Nicole Tasch, Annegret Schneemann, Britta Dreier, Martina Balleininger (all from G tingen), William C. Lamanna, Jaqueline Alonso Lunar, Kerstin B er, and Claudia Prange for S1PR1 Modulator site technical help; Markus Damme for initial analysis of subcellular localization; and Jeffrey Esko (San Diego) for PLD Inhibitor Storage & Stability critically reading the manuscript. We also thank Kurt von Figura for support in the course of the initial phase of this project.Dierks, T. (2007) The heparanome. The enigma of encoding and decoding heparan sulfate sulfation. J. Biotechnol. 129, 290 ?07 Schmidt, B., Selmer, T., Ingendoh, A., and von Figura, K. (1995) A novel amino acid modification in sulfatases that may be defective in several sulfatase deficiency. Cell 82, 271?78 von B ow, R., Schmidt, B., Dierks, T., von Figura, K., and Us , I. (2001) Crystal structure of an enzyme-substrate complex gives insight in to the interaction amongst human arylsulfatase A and its substrates through catalysis. J. Mol. Biol. 305, 269 ?77 Dierks, T., Lecca, M. R., Schlotterhose, P., Schmidt, B., and von Figura, K. (1999) Sequence determinants directing conversion of cysteine to formylglycine in eukaryotic sulfatases. EMBO J. 18, 2084 ?091 Dierks, T., Schmidt, B., and von Figura, K. (1997) Conversion of cysteine to formylglycine. A protein modification within the endoplasmic reticulum. Proc. Natl. Acad. Sci. U.S.A. 94, 11963?1968 Dierks, T., Dickmanns, A., Preusser-Kunze, A., Schmidt, B., Mariappan, M., von Figura, K., Ficner, R., and Rudolph, M. G. (2005) Molecular basis for several sulfatase deficiency and mechanism for formylglycine generation on the human formylglycine-generating enzyme. Cell 121, 541?52 Dierks, T., Schmidt, B., Borissenko, L. V., Peng, J., Preusser, A., Mariappan, M., and von Figura, K. (2003) Many sulfatase deficiency is triggered by mutations in the gene encoding the human C( )-formylglycine producing enzyme. Cell 113, 435?444 Dierks, T., Schlotawa, L., Frese, M. A., Radhakrishnan, K., von Figura, K., and Schmidt, B. (2009) Molecular basis of various sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease. Lysosomal storage issues brought on by defects of non-lysosomal proteins. Biochim. Biophys. Acta 1793, 710 ?25 Cosma, M. P., Pepe, S., Annunziata, I., Newbold, R. F., Grompe, M., Parenti, G., and Ballabio,.
