MAG

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Myelin-associated glycoprotein (MAG, Siglec-4) is unique among the siglecs in that it is expressed exclusively on neuronal glial cells[1][2]. It is the most highly conserved among the siglecs in mammalian species. This siglec paradigm is unique in its activity for stabilizing axon-myelin interactions. MAG has a cytoplasmic domain that is devoid of ITIMs, but contains a tyrosine-based motif associated with binding the FYN tyrosine kinase, believed to play a role in its activity in myelin-axon interactions. MAG recognizes as ligands sialoside sequences found on gangliosides that are abundant in axonal membranes[2]. It is one of several proteins in myelin that negatively regulate axon outgrowth following tissue injury, an activity that involves MAG ligand interactions. Evidence suggests that inhibition of MAG ligand interactions may enhance neurite outgrowth and repair of injured neurons[18,19][3][4].

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

Several CFG Participating Investigators (PIs) have contributed to identification of MAG as a siglec and to understanding the functions of MAG, including: Paul Crocker, Sørge Kelm, James Paulson, Ronald Schnaar

Progress toward understanding this GBP paradigm

Carbohydrate ligands


Cellular expression


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for Siglec-4.

Glycan profiling


Glycogene microarray


Knockout mouse lines

The CFG has phenotyped the MAG-deficient mouse.

Glycan array

Investigators have used CFG carbohydrate compounds to study MAG ligand specificity.

Related GBPs

None.

References

  1. Crocker, P. R., Paulson, J. C. & Varki, A. Siglecs and their roles in the immune system. Nat Rev Immunol 7, 255-266 (2007).
  2. 2.0 2.1 Schnaar, R. L. Brain gangliosides in axon-myelin stability and axon regeneration. FEBS Lett (2009).
  3. Yang, L. J. et al. Sialidase enhances spinal axon outgrowth in vivo. Proc Natl Acad Sci U S A 103, 11057-11062 (2006).
  4. Vyas, A. A., Blixt, O., Paulson, J. C. & Schnaar, R. L. Potent glycan inhibitors of myelin-associated glycoprotein enhance axon outgrowth in vitro. J Biol Chem 280, 16305-16310 (2005).

Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Paul Crocker, James Paulson

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