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Published online April 30, 2007
doi:10.1083/jcb.200702102
The Journal of Cell Biology, Vol. 177, No. 3, 393-399
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Venkatesh et al.
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Molecular dissection of the myelin-associated glycoprotein receptor complex reveals cell type–specific mechanisms for neurite outgrowth inhibition

Karthik Venkatesh1,2,3, Onanong Chivatakarn1,2,3, Shey-Shing Sheu4, and Roman J. Giger2,3

1 Interdepartmental Graduate Program in Neuroscience, 2 Center for Aging and Developmental Biology, 3 Department of Biomedical Genetics, and 4 Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642

Correspondence to Roman J. Giger: Roman_Giger{at}URMC.Rochester.edu

Neuronal Nogo66 receptor-1 (NgR1) binds the myelin inhibitors NogoA, OMgp, and myelin-associated glycoprotein (MAG) and has been proposed to function as the ligand-binding component of a receptor complex that also includes Lingo-1, p75NTR, or TROY. In this study, we use Vibrio cholerae neuraminidase (VCN) and mouse genetics to probe the molecular composition of the MAG receptor complex in postnatal retinal ganglion cells (RGCs). We find that VCN treatment is not sufficient to release MAG inhibition of RGCs; however, it does attenuate MAG inhibition of cerebellar granule neurons. Furthermore, the loss of p75NTR is not sufficient to release MAG inhibition of RGCs, but p75NTR–/– dorsal root ganglion neurons show enhanced growth on MAG compared to wild-type controls. Interestingly, TROY is not a functional substitute for p75NTR in RGCs. Finally, NgR1/ RGCs are strongly inhibited by MAG. In the presence of VCN, however, NgR1/ RGCs exhibit enhanced neurite growth. Collectively, our experiments reveal distinct and cell type–specific mechanisms for MAG-elicited growth inhibition.

Abbreviations used in this paper: CGN, cerebellar granule neuron; CNS, central nervous system; DRG, dorsal root ganglion; MAG, myelin-associated glycoprotein; NgR, neuronal Nogo66 receptor; RGC, retinal ganglion cell; VCN, Vibrio cholerae neuraminidase.


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