Nerve cells or neurons in the brain can pass signals to up to another 10 000 neurons via synapses. Moreover, dynamic synaptic plasticity may well lie at the heart of memory formation. Here at the neural membrane of these all-important junctions, a cytoskeleton network of microtubules and actin interact with the molecular motor proteins -kinesin, dynein and myosin. Defects in the cargo-transporting function of molecular motors are a common feature of many neurodegenerative and psychiatric diseases. The EU-funded NEUROTRAF (Molecular mechanisms of synapto-dendritic cargo trafficking) project has developed new molecular tools and imaging systems to look at this machinery in living neurons. Harnessing immunofluorescent nanoprobes attached to quantum dots enabled the researchers to track motor proteins with nanometre precision. The details of intracellular processes such as the behaviour of motor-coupled cargo in neurons can be viewed and steered using this technology. Moreover, scientists could resolve dendritic microtubules in hippocampal neurons to determine how dendrites are assembled and maintained. Dendritic spines help transmit signals to a nerve cell body and NEUROTRAF observed how cargo is transmitted between spines. Using the new tools, the researchers determined how the calcium2+-sensor caldendrin impacts actin dynamics in spines. Required for organisation of axonal microtubules, mutations in KIF1 binding protein (KBP) are responsible for the severe neurological disorder, Goldberg-Shprintzen (GOSH) syndrome. Research results showed that KBP regulates motor activity by preventing kinesin movement along microtubules. This has uncovered a novel mechanism for modulating activity of kinesin motors and suggests that altered synaptic vesicle trafficking contributes to GOSH. NEUROTRAF research has resulted in the preparation and submission of at least three scientific papers. The results have contributed to a significant knowledge platform on molecular involvement in memory formation and development of neurological disorders.
Molecular machinery, memory, learning, cytoskeleton, molecular motor proteins, quantum dot, caldendrin, KBP, GOSH