This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Sulfs are a family of extracellular endosulfatases that modify heparan sulfate (HS) chains at cell surfaces and in extracellular matrices. They release sulfate groups at the 6-O-position of a subset of glucosamine residues in HS chains. The activity of Sulf enzymes serves to potentiate activities of growth factors including GDNF, BMP, Shh, and Wnt and to reduce activities of FGF2, HP-EGF, HGF, and TGF-?. As a result of these activities and depending on the context, Sulfs have been observed to serve as oncogenic effectors and as tumor suppressors. Sulf activities appear to induce changes in expression of biosynthetic enzymes, resulting in changes in expressed HS structure that do not necessary reflect the direct Sulf enzymatic activity. As a result, the influences of Sulf activity on cellular phenotype are complex. The goals of this work are to (1) define the HS structural phenotype in mouse embryonic fibroblast cells as a function of Sulf enzyme knockout at both the HS disaccharide and oligosaccharide levels. These results will be compared against those obtained using recombinant Sulf enzymes on purified HS. Progress update: We have published two collaborative papers on the structural phenotypes of HS related to the spermatogonal stem cell niche (1) and the glomerular filtration barrier (2) in Sulf knockout mice. 1. Langsdorf, A., Schumacher, V., Shi, X., Tran, T., Zaia, J., Jain, S., Taglienti, M., Kreidberg, J. A., Fine, A., and Ai, X. (2010) Expression regulation and function of Sulfs in the spermatogonial stem cell niche, Glycobiology 21, 152-161. 2. Schumacher, V., Schlotzer-Schrehardt, U., Karumanchi, S. A., Shi, X., Zaia, J., Jeruschke, S., Zhang, D., Pavenstaedt, H., Drenckhan, A., Amann, K., Ng, C., Hartwig, S., Ng, K.-H., Ho, J., Kreidberg, J. A., Taglienti, M., Royer-Pokora, B., and Ai, X. (2011) WT1 regulation of Sulf expression is crucial to maintaining the glomerular filtration barrier, Journal of the American Society for Nephrology Accepted 2/22/11.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR010888-15
Application #
8365568
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (40))
Project Start
2011-06-01
Project End
2012-08-09
Budget Start
2011-06-01
Budget End
2012-08-31
Support Year
15
Fiscal Year
2011
Total Cost
$12,304
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Hu, Han; Khatri, Kshitij; Zaia, Joseph (2017) Algorithms and design strategies towards automated glycoproteomics analysis. Mass Spectrom Rev 36:475-498
Sethi, Manveen K; Zaia, Joseph (2017) Extracellular matrix proteomics in schizophrenia and Alzheimer's disease. Anal Bioanal Chem 409:379-394
Hu, Han; Khatri, Kshitij; Klein, Joshua et al. (2016) A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J 33:285-96
Ji, Yuhuan; Bachschmid, Markus M; Costello, Catherine E et al. (2016) S- to N-Palmitoyl Transfer During Proteomic Sample Preparation. J Am Soc Mass Spectrom 27:677-85
Pu, Yi; Ridgeway, Mark E; Glaskin, Rebecca S et al. (2016) Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry. Anal Chem 88:3440-3
Wang, Yun Hwa Walter; Meyer, Rosana D; Bondzie, Philip A et al. (2016) IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function. J Mol Biol 428:5019-5033
Srinivasan, Srimathi; Chitalia, Vipul; Meyer, Rosana D et al. (2015) Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis 18:449-62
Yu, Xiang; Sargaeva, Nadezda P; Thompson, Christopher J et al. (2015) In-Source Decay Characterization of Isoaspartate and ?-Peptides. Int J Mass Spectrom 390:101-109
Steinhorn, Benjamin S; Loscalzo, Joseph; Michel, Thomas (2015) Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med 373:277-80
Walsh, Erica M; Niu, MengMeng; Bergholz, Johann et al. (2015) Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation. Biochem Biophys Res Commun 461:293-9

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