The development of the nervous system depends on the right balance of factors that promote and inhibit the growth of neurons—the cell that processes and transmits information in the nervous system–and determines the number, size and direction of their growth. Disruptions in this balance can lead to neurological disorders, such as multiple sclerosis. In a recent study published in Developmental Cell led by TWRI Scientist Dr. Philippe Monnier, researchers uncovered novel forms of the protein repulsive guidance molecule (RGMa) and its implications on the regulation of neuronal growth.

Dr. Monnier’s group discovered that RGMa is cut, or cleaved, by the proteins SKI-1 and Furin, producing seven forms of the protein. Interestingly, six forms are able to inhibit neuronal growth through interaction with another protein, Neogenin. Together, these proteins contribute towards the proper guidance of neuronal growth and development.

“These results have important implications for our understanding of the regulation of neuronal growth,” explains Dr. Monnier. “Uncovering multiple forms of RGMa and how they function in the cell will help with the development of novel therapeutics that target neuronal growth in the treatment of disease.”

SKI-1 and Furin generate multiple RGMa fragments that regulate axonal growth. Tassew NG, Charish J, Seidah NG, Monnier PP. Developmental Cell. 2012 Feb 14. [Pubmed abstract]

This work was supported by the Heart and Stroke Foundation of Ontario and the Canadian Institutes of Health Research.