Special DeliveryMotor Protein Vital in Connecting NeuronsA motor protein called myosin X runs the main road of a developing neuron, delivering to its tip a receptor that enables it to communicate with other neurons, scientists say. In another piece of the puzzle of how neurons form connections, researchers have found myosin X travels a portion of a neuron’s backbone called the actin filament, a sort of highway in the cell’s highest traffic area, said Dr. WenCheng Xiong, an MCG developmental neurobiologist. Part of its cargo is DCC receptor, which needs to move from the central nucleus where it is synthesized to the cell’s periphery, Dr. Xiong and her colleagues reported in the February 2007 issue of Nature Cell Biology. The paper was recently featured in the Editor’s Choice section of Science Magazine’s Signal Transduction Knowledge Environment site (www.stke.org) as a noteworthy contribution to scientific literature. At the periphery, DCC interacts with netrin1, a guidance cue for helping the armlike extension of the cell, called the axon, grow in the right direction. Cells eventually communicate through synapses at the end of these cellular projections. “During early development, axons need to find a target, decide how long to grow and in which direction to grow. Eventually, they will form a synapse,” said Dr. Xiong, who hopes a better understanding of the process will help restore communication in spinal cord patients. “Growth is precisely controlled during development,” she said, ensuring proper brain wiring and connectivity. “Myosin X gets the DCC receptor where it needs to be so it can interact with netrin1.” Her previous studies, published in 2004 in Nature Neuroscience, showed that DCC binding to netrin1 activates an enzyme, focal adhesion kinase, enabling developing cells to reorganize and know how to move. The process enables brain cells to reach out to each other and across the midline of the developing brain and spinal cord. When the kinase is deleted, the axon doesn’t make the proper connections. When researchers cut off myosin X’s motor—which they believe happens in spinal cord injuries—axon outgrowth also was hindered. “Myosin X plays a critical role in neurons during development,” said Dr. Xiong. Different versions of the myosin family proteins are critical to essentially every cell. The rapidly moving protein is easily degraded and needs tight regulation. “If you don’t want to have dramatic changes in your neuron structure, you don’t want this molecule,” Dr. Xiong said. In fact, she suspects the function of myosin X changes as the neuron develops. She has documented that late in development, when the axon should stop growing, a shorter molecule, minus the motor, is expressed. “Probably after the neuron is developed, the major work of myosin is done. There are many cleavage sites in the middle, and this typically large molecule can be cut down to a small molecule that actually inhibits axon growth function,” Dr. Xiong said. She suspects that negative function surfaces when the spinal cord is cut and plans to examine whether the protein is degraded in spinal cord injuries. “We already have evidence that if this protein degrades, most frequently without its motor domain, it becomes negative, inhibits DCC getting to the proper place and so axonal growth,” Dr. Xion |