Glycolipid-mediated cell–cell recognition in inflammation and nerve regeneration

doi:10.1016/j.abb.2004.02.019

Archives of Biochemistry and Biophysics

Volume 426, Issue 2, 15 June 2004, Pages 163-172

https://doi.org/10.1016/j.abb.2004.02.019 Get rights and content

Abstract

Cell surface complex carbohydrates have emerged as key recognition molecules, mediating physiological interactions between cells. Typically, glycans on one cell surface are engaged by complementary carbohydrate binding proteins (lectins) on an apposing cell, initiating appropriate cellular responses. Although many cell surface lectins have been identified in vertebrates, only a few of their endogenous carbohydrate ligands have been established. Each major class of cell surface glycans—glycoproteins, glycolipids, and proteoglycans—has been implicated as physiologically relevant lectin ligands. The current minireview focuses on findings that implicate glycosphingolipids as especially important molecules in cell–cell recognition in two different systems: the recognition of human leukocytes by E-selectin on the vascular endothelium during inflammation and the recognition of nerve cell axons by myelin-associated glycoprotein in myelin–axon stabilization and the regulation of axon regeneration.

Section snippets

Selectins in inflammation

Selectins cooperate to initiate the inflammatory response, in which circulating neutrophils bind to activated vascular endothelium, then extravasate into the adjoining tissue [11]. Extensive data support a three-step molecular model for specifying extravasation [12]. (i) Under the shear stresses associated with blood flow, initial tethering and rolling of neutrophils on activated endothelium is mediated by the recognition of glycoconjugates on the circulating neutrophil surface by selectins

Brain gangliosides

The brain is unusual for its preponderance of glycosphingolipids. Of the total glycoconjugate-bound carbohydrate in the brain, 81% is glycolipid, 17% glycoprotein, and 2% proteoglycan [48]. Brain glycolipids exist in two quantitatively major classes, the galactosylceramides, key structural components of myelin, and gangliosides, which are major cell surface glycans on both nerve cells and glia. Of particular interest in the study of vertebrate lectins are the gangliosides, which are the

Conclusion

Since the first hints that cell surface carbohydrates might play crucial roles in cell–cell recognition four decades ago [10], our appreciation of the richness of glycan structural diversity and the mechanisms by which that diversity is translated into physiological effects have grown tremendously. Glycobiology is now well integrated into our understanding of the development and functioning of multicellular organisms. As ubiquitous cell surface glycans, glycolipids are taking their place,

Acknowledgements

Research on inflammation and axon regeneration in the Schnaar laboratory is supported by Grants AI045115 and NS037096 from the National Institutes of Health.

References (88)

P.R Crocker
Curr. Opin. Struct. Biol.
(2002)
G.A Rabinovich et al.
Trends Immunol.
(2002)
J.L Magnani et al.
Anal. Biochem.
(1980)
H.C Krivan et al.
Arch. Biochem. Biophys.
(1988)
T.A Springer
Cell
(1994)
T Marquardt et al.
J. Pediatr.
(1999)
T Marquardt et al.
Blood
(1999)
K Luhn et al.
Blood
(2001)
L.M Stoolman
Cell
(1989)
J.B Lowe et al.
Cell
(1990)

W.S Somers et al.

Cell

(2000)

A Leppanen et al.

J. Biol. Chem.

(2000)

S.D Rosen

Am. J. Pathol.

(1999)

C.B Fieger et al.

J. Biol. Chem.

(2003)

M.M Kobzdej et al.

Blood

(2002)

G.R Larsen et al.

J. Biol. Chem.

(1992)

J.B Lowe et al.

J. Biol. Chem.

(1991)

M.R Stroud et al.

Biochem. Biophys. Res. Commun.

(1995)

P Swank-Hill et al.

Anal. Biochem.

(1987)

M.M Burdick et al.

Biochem. Biophys. Res. Commun.

(2001)

P.W Johnson et al.

Neuron

(1989)

G Mukhopadhyay et al.

Neuron

(1994)

L McKerracher et al.

Neuron

(1994)

S Bartsch et al.

Brain Res.

(1997)

Y.J Shen et al.

Mol. Cell Neurosci.

(1998)

M Schäfer et al.

Neuron

(1996)

K Torigoe et al.

Exp. Neurol.

(1998)

S Kelm et al.

Curr. Biol.

(1994)

J.L Magnani et al.

Methods Enzymol.

(1982)

G.C Hansson et al.

Anal. Biochem.

(1985)

L.J.S Yang et al.

Anal. Biochem.

(1996)

B.E Collins et al.

J. Biol. Chem.

(1997)

B.E Collins et al.

J. Biol. Chem.

(1997)

S Chiavegatto et al.

Exp. Neurol.

(2000)

H Kawai et al.

J. Biol. Chem.

(2001)

M Vinson et al.

J. Biol. Chem.

(2001)

M Vinson et al.

Mol. Cell Neurosci.

(2003)

G Tettamanti et al.

Biochim. Biophys. Acta

(1973)

J.A Alhadeff et al.

Int. J. Biochem.

(1982)

O Nilsson et al.

J. Lipid Res.

(1982)

R.L Schnaar et al.

Anal. Biochem.

(2002)

M.E Taylor et al.

Introduction to Glycobiology

(2003)

S Hakomori

Proc. Natl. Acad. Sci. USA

(2002)

K Drickamer et al.

Biochem. Soc. Symp.

(2002)

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^☆: Dedicated, with sincere appreciation, to the memory of Dr. Victor Ginsburg, whose insights and enthusiasm helped shape the development of glycobiology.

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MinireviewGlycolipid-mediated cell–cell recognition in inflammation and nerve regeneration☆

Abstract

Section snippets

Selectins in inflammation

Brain gangliosides

Conclusion

Acknowledgements

Curr. Opin. Struct. Biol.

Trends Immunol.

Anal. Biochem.

Arch. Biochem. Biophys.

Cell

J. Pediatr.

Blood

Blood

Cell

Cell

Cell

J. Biol. Chem.

Am. J. Pathol.

J. Biol. Chem.

Blood

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Anal. Biochem.

Biochem. Biophys. Res. Commun.

Neuron

Neuron

Neuron

Brain Res.

Mol. Cell Neurosci.

Neuron

Exp. Neurol.

Curr. Biol.

Methods Enzymol.

Anal. Biochem.

Anal. Biochem.

J. Biol. Chem.

J. Biol. Chem.

Exp. Neurol.

J. Biol. Chem.

J. Biol. Chem.

Mol. Cell Neurosci.

Biochim. Biophys. Acta

Int. J. Biochem.

J. Lipid Res.

Anal. Biochem.

Introduction to Glycobiology

Proc. Natl. Acad. Sci. USA

Biochem. Soc. Symp.

Minireview
Glycolipid-mediated cell–cell recognition in inflammation and nerve regeneration☆