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Publication : Distinct contributions of Galgt1 and Galgt2 to carbohydrate expression and function at the mouse neuromuscular junction.

First Author  Singhal N Year  2012
Journal  Mol Cell Neurosci Volume  51
Issue  3-4 Pages  112-26
PubMed ID  22982027 Mgi Jnum  J:203675
Mgi Id  MGI:5528454 Doi  10.1016/j.mcn.2012.08.014
Citation  Singhal N, et al. (2012) Distinct contributions of Galgt1 and Galgt2 to carbohydrate expression and function at the mouse neuromuscular junction. Mol Cell Neurosci 51(3-4):112-26
abstractText  At the mammalian neuromuscular junction (NMJ), the CT (cytotoxic T cell) carbohydrate antigen [GalNAcbeta1,4[Neu5Ac/Gcalpha2,3]Galbeta1,4GlcNAc-] is a unique synaptic cell surface carbohydrate present in both the presynaptic and postsynaptic membranes. Here we show that Galgt1, which synthesizes the beta1,4GalNAc linkage of the CT carbohydrate on gangliosides, is required for presynaptic expression of the CT carbohydrate at the NMJ, while Galgt2, which can synthesize the beta1,4GalNAc of the CT carbohydrate on glycoproteins, is required for postsynaptic expression. Proper postsynaptic localization of the CT carbohydrate also required muscle expression of dystroglycan, a known muscle substrate for Galgt2. Transgenic overexpression of Galgt2 in skeletal myofibers altered the expression of synaptic muscle proteins and altered neuromuscular topography, which was partially NCAM-dependent, while an increase in postsynaptic AChR-rich domains was observed in both neuron- and skeletal muscle-specific Galgt2 transgenic mice. By contrast, overexpression of Galgt1 in muscle did not allow for increased expression of CT carbohydrate on the sarcolemmal membrane and instead caused muscle pathology. Loss of Galgt2 increased intracellular accumulation of acetylcholine receptors and acetylcholinesterase within skeletal myofibers, suggesting an additional role for Galgt2 in neuromuscular stability. These experiments demonstrate that Galgt1 and Galgt2 contribute in distinct ways to the expression and function of synaptic betaGalNAc-containing carbohydrates at the NMJ.
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