CD15 expression in human myeloid cell differentiation is regulated by sialidase activity

Samah Zeineb Gadhoum; Robert Sackstein

doi:10.1038/nchembio.116

CD15 expression in human myeloid cell differentiation is regulated by sialidase activity

Samah Zeineb Gadhoum, Robert Sackstein^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

The glycan determinant CD15 (also known as Lewis x, or Le^x) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of α(2-3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLe^x or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant.

Original language	English (US)
Pages (from-to)	751-757
Number of pages	7
Journal	Nature Chemical Biology
Volume	4
Issue number	12
DOIs	https://doi.org/10.1038/nchembio.116
State	Published - Dec 2008
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to D. Floyd, S. Hamdan, C. Silvescu and C. Knoblauch for technical support, to J. Merzaban, N. Stamatos, C. Dimitroff and M. Burdick for helpful discussions of the manuscript, and to I. Galinsky, R. Stone, D. DeAngelo, M. Wadleigh and A. Sirulnik for assistance in procuring leukemia samples. This work was supported by US National Heart, Lung, and Blood Institute grant RO1 HL60528 (R.S.), US National Institute of Diabetes and Digestive and Kidney Diseases grant R21 DK075012 (R.S.) and the Team Jobie Leukemia Research fund (R.S.).

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/nchembio.116

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title = "CD15 expression in human myeloid cell differentiation is regulated by sialidase activity",

abstract = "The glycan determinant CD15 (also known as Lewis x, or Lex) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of α(2-3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLex or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant.",

author = "Gadhoum, {Samah Zeineb} and Robert Sackstein",

note = "Funding Information: We are grateful to D. Floyd, S. Hamdan, C. Silvescu and C. Knoblauch for technical support, to J. Merzaban, N. Stamatos, C. Dimitroff and M. Burdick for helpful discussions of the manuscript, and to I. Galinsky, R. Stone, D. DeAngelo, M. Wadleigh and A. Sirulnik for assistance in procuring leukemia samples. This work was supported by US National Heart, Lung, and Blood Institute grant RO1 HL60528 (R.S.), US National Institute of Diabetes and Digestive and Kidney Diseases grant R21 DK075012 (R.S.) and the Team Jobie Leukemia Research fund (R.S.).",

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N2 - The glycan determinant CD15 (also known as Lewis x, or Lex) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of α(2-3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLex or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant.

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CD15 expression in human myeloid cell differentiation is regulated by sialidase activity

Abstract

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