A Long and Winding Road

Long distance messengers star in many heroic tales, perhaps the most famous being the one about the runner who carried the news about the victory of the Greeks over the Persians in the fateful battle of Marathon. A team of researchers at the Weizmann Institute of Science has now discovered how molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves.

A nerve cell has a cell body and a long extension, called an axon, which in humans can reach up to one meter in length. Nerve cells belonging to the peripheral nervous system can regrow when their axons are damaged. But how does the damaged axon inform the cell body that it must start producing vital proteins for the healing? That’s precisely where the molecular messengers, proteins called Erk-1 and Erk-2, enter the picture. When the axon is injured, these proteins bind to molecules of phosphorus. In this phosphorylated state, they can communicate to command centers in the cell, transmitting a message that activates certain genes in the cell body, which then manufactures proteins that are vital for the healing of the injured axon. The problem is that the messengers must transmit their phosphorus message over a great distance along the axon, and in the course of this arduous journey can easily lose their phosphorus en route.

Dr. Michael Fainzilber and graduate students Eran Perlson and Shlomit Hanz of the Weizmann Institute’s Biological Chemistry Department found that the Erk messengers, together with their phosphorus message, bind to a special molecule called vimentin, which protects them from dismantling or loss of the phosphorus. Vimentin links up to motor proteins that carry the message along the axon, and thanks to this linkage and protection, the messengers can safely transmit their message, thus bringing the injured axon’s call for help to the cell body. The study appears in the March 3 issue of Neuron. The scientists hope that these findings might advance the future search for new therapies for injured nerve fibers.

The research team also included Prof. Rony Seger of the Biological Regulation Department, Prof. Michael Elbaum of the Materials and Interfaces Department, graduate students Keren Ben Yaakov and Yael Segal-Ruder of the Biological Chemistry Department, and postdoctoral fellow Dr. Daphna Frenkiel-Krispin of the Materials and Interfaces Department.

Dr. Michael Fainzilber’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; Mr. and Mrs. Alan Fischer, Larchmont, NY; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Irwin Green Alzheimer's Research Fund and the Buddy Taub Foundation.

Dr. Fainzilber is the incumbent of the Daniel E. Koshland Sr. Career Development Chair.