If the body of a nerve cell were a meter wide, some of its extensions, called axons, would stretch for dozens of miles. Yet signaling molecules, as well as other substances made in the body of the cell, are effectively transported along these axons.
Until now, such molecules were known to “ride” to the end of an axon along a rigid internal framework known as the cytoskeleton.
Weizmann Institute scientists have now demonstrated the existence of an entirely new means of transportation inside nerve cells. They showed that molecules can also travel in the cell’s endoplasmic reticulum – a large cellular compartment known to store or even manufacture various chemicals – that envelops the nucleus but also extends along the cytoskeleton to various parts of the cell. This discovery, recently published in PLoS Biology,
emerged from research conducted by graduate student Shaul Yogev with Dr. Eyal Schejter in the laboratory of Prof. Ben-Zion Shilo
of the Molecular Genetics Department.
The scientists focused on a signaling molecule that is crucial for communication between the eye and the brain in fruit fly larvae. They found that this signaling molecule, a type of epidermal growth factor, travels from the body of the nerve cell to the tip of the axon inside the endoplasmic reticulum. It is accompanied by two helpers: a “chaperone” that protects it from damage and an enzyme that clips the signaling molecule as it reaches the tip of the axon, so that it can leave the nerve cell.
The researchers then tried removing the clipping enzyme from the endoplasmic reticulum, preventing the release of the signaling molecule. They thus confirmed that the molecule’s regular route should indeed be through the reticulum and not through any other part of the cell.
Though the study was conducted in the fruit fly, its findings are thought to apply to mammals, including humans. Clarifying how signals are transported in nerve cells is crucial for understanding their functioning in health and disease.
Prof. Ben- Zion Shilo's research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Carolito Stiftung; la Fondation Raphael et Regina Levy; and the estate of Georg Galai. Prof. Shilo is the incumbent of the Hilda and Cecil Lewis Professorial Chair of Molecular Genetics.