When you touch a hot object,the sensory receptors in your neurons take stock of the increased skin temperature at the point of contact and convert this information into electrical signals. These are sent through the neuronal network to the brain,which then signals motor neurons to move your hand away. All this happens in a split-secondif it didnt,youd be roast meat. To understand how neurons handle our interface with the world so effectively,it is important to look at how they communicate amongst themselves. The human brain has about 200 billion neurons,most of which have branching dendrites that collect information,and synapses,which communicate this information to neighbouring neurons. Since neurons are extremely elongated cells,these synaptic junctions are often a metre away from the cell body,connected by a stem called the axon. Think of the cell body as the root where proteins,lipids,mitochondria,neurotransmitters and RNA are produced,and the synapse as the leaf to which these nutrients must be delivered. If the stem is severed,the leaf withers away. In neurons,too,problems in transportation are being increasingly linked to neurodegenerative diseases like Alzheimers disease,amyotrophic lateral sclerosis (ALS) and Huntingtons disease. At the National Centre for Biological Sciences in Bangalore,Sandhya P. Koushika studies axonal transport using C. elegans,a tiny worm found in soil that is a useful model to study fundamental biological processes. Her lab has developed novel ways of imaging live transportation processes in the worm and arrived at useful insights on the inner workings of neurons. Transporting cargo from the cell body to the synapse would take days,were it not for molecular motors,a class of proteins that attach themselves to cargo. They are like lorries navigating an Indian road,finding their way out of traffic jams and doing all they can to reach their destination and deliver the goods, Koushika says. The axonal highway is made up of a ladder of polymers called microtubules and it witnesses constant to-and-fro movement of energy-producing mitochondria and of vesiclesbubbles made of a lipid bilayer that contain proteins and neurotransmitters essential to the functioning of the neuron. While it has been known that defects in delivery of cargo to the synapse can induce neurodegeneration,recent research suggests that defects in retrograde transport (from the synapse back to the cell body),too,correlate with progressive neuronal cell death. Quality control is very important in neurons. When proteins get used up at the synapse,they are sent back to the cell body as garbage to be degraded, says Koushika,who co-authored a 2004 paper in the Journal of Neuroscience,showing that C. elegans mutants with defective retrograde transport had ALS-type phenotypes. Looking at mouse models,people suspect that if you restore the transport mechanism,cells can live longer, she adds. There have also been partially successful attempts at delivering drugs along the retrograde pathway,but such solutions are yet to be brought into the mainstream,partly because the process of retrograde transport itself is yet to be well understood. In a recent study published in the journal Traffic,Koushikas lab developed a means to attach tags to retrograde cargo,so that retrograde transport can be filmed and analysed in real time. The axonal highway is directional,and so are the motors that attach to cargo,which means that different motors drive anterograde and retrograde transportbroadly,kinesins are the motors used for forward motion and dyneins are the ones used for backward motion. Over 60 different molecular motors have been identified in humans,and even C. elegans,which has just 302 neurons,uses 22 motors. A lot is still unknown about motorshow are motors matched with appropriate cargo,how do they share cargo,and how do they know when to unload? Koushika and her colleagues have answered one such questionwhat happens to motors once they have delivered the cargo? Koushikas lab was the first to demonstratein a 2010 paper in the journal PLoS Geneticsthat molecular motors are single-use and that they may get degraded at the synapse. Unlike vesicular casing,which is reused a few times before being degraded,motors are used up during transport, Koushika says. Gautam Menon,professor at the Institute of Mathematical Sciences,Chennai,who works with Koushika on modelling axonal transport,says they have observed and modelled several interesting results. No one has thought of looking at why clusters form along the axonal path. We find that clusters come about when vesicles moving at opposite directions encounter each other. And that when there is a roadblock ahead,vesicles do one of many thingsthey try to move to an unoccupied lane or wait in line till the jam clears or,with a change of motors,go back the way they came. If thats not exactly like driving on Indian roads,what is?
