Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins.

Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Research Abstract Details 

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Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Abstract Text:

David E Sleat,Yanhong Wang,Istvan Sohar,Henry Lackland,Yan Li,Hong Li,Haiyan Zheng,Peter Lobel,

Acid hydrolase activities are normally confined within the cell to the lysosome, a membrane-delimited cytoplasmic organelle primarily responsible for the degradation of macromolecules. However, lysosomal proteins are also present in human plasma, and a proportion of these retain mannose 6-phosphate (Man-6-P), a modification on N-linked glycans that is recognized by Man-6-P receptors (MPRs) that normally direct the targeting of these proteins to the lysosome. In this study, we purified the Man-6-P glycoforms of proteins from human plasma by affinity chromatography on immobilized MPRs and characterized this subproteome by two-dimensional gel electrophoresis and by tandem mass spectrometry. As expected, we identified many known and potential candidate lysosomal proteins. In addition, we also identified a number of abundant classical plasma proteins that were retained even after two consecutive rounds of affinity purification. Given their abundance in plasma, we initially considered these proteins to be likely contaminants, but a mass spectrometric study of Man-6-phosphorylation sites using MPR-purified glycopeptides revealed that some proportion of these classical plasma proteins contained the Man-6-P modification. We propose that these glycoproteins are phosphorylated at low levels by the lysosomal enzyme phosphotransferase, but their high abundance results in detection of Man-6-P glycoforms in plasma. These results may provide useful insights into the molecular processes underlying Man-6-phosphorylation and highlight circumstances under which the presence of Man-6-P may not be indicative of lysosomal function. In addition, characterization of the plasma Man-6-P glycoproteome should facilitate development of mass spectrometry-based tools for the diagnosis of lysosomal storage diseases and for investigating the involvement of Man-6-P-containing glycoproteins in more widespread human diseases and their potential utility as biomarkers.

Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Publishing Authors By Initials

DE Sleat,Y Wang,I Sohar,H Lackland,Y Li,H Li,H Zheng,P Lobel,

For similar investigative techniques: epidemiologic methods: epidemiologic research design: reproducibility of results research abstracts see: investigative techniques: epidemiologic methods: epidemiologic research design: reproducibility of results research

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Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular & cellular proteomics : MCP

VOLUME: 5

Page Numbers: 1942-56

Journal Abbreviation: Mol. Cell Proteomics

ISSN: 1535-9476

DAY: 17

MONTH: 05

YEAR: 2006

Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101125647

Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Keywords Mesh Terms:

KEYWORDS: Reproducibility of Results

MESH TERMS: analysis

Chemical & Substance for Abstract: Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Information

Substance Name: mannose-6-phosphate

Registry Number: 3672-15-9

Grant and Affiliation Information for Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins.

AFFILIATION: Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey, Piscataway, 08854, USA.

Country: United States

AGENCY: United States NCRR

GRANT: S10RR017992

ACRONYM: RR

MEDLINETA: Mol Cell Proteomics

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