As a miner's son growing up in Kiriburu, a village in West Singbhum disrict in Jharkhand, which is known for its iron ore mines, Bikash Choudhary was fascinated by what he saw: truck fter truck loaded with the re leaving for the process ng plant miles away and re urning empty. It was the ame every day , for years.
Two decades later, Choudhary , now a graduate student t the National Centre for Biological Sciences (NCBS), Bangalore, is passionately racking a different kind of argo -but inside the brain.
About two years ago, Choudhary joined a senior doctoral student, Jitendra Kumar, and Sandhya Koushika, professor of neurobiolo y at the NCBS. Significantly, Choudhary and Kumar, who hails from a remote village in Patna district in Bihar, have lot in common. Both are the irst in their families to pur ue scientific research. Kumar and Koushika have been studying the mechanisms involved in passing on instructions from the brain to the other organs since 2005. The NCBS scientists recently showed that when it comes to the brain cells of living organisms, the traffic is one way -the vehicles that haul the cargo (or instructions) are ruthlessly destroyed after the delivery.
"It's like having to make new vehicles each time you have a cargo to ship," says Kumar.
The finding, reported in the journal PLoS Genetics last week, may help resolve a mystery that has baffled scientists for almost a quarter of a century. Both Kumar and Choudhary have contributed equally to the work, which unravels a remarkable facet of a class of proteins called kinesins.
Discovered in 1984, kinesins -molecular motors that move chromosomes and other cargo inside the cell -play a key role in a number of important cellular functions such as cell division and cell multiplication. "A cell is like a city. If material can't be moved from the cell's factory to where it is needed, the cell cannot function," says Shubha Tole, a neuroscientist at the Tata Institute of Fundamental Research, Mumbai.
In the last two decades, researchers have not only identified many types of kinesins and kinesin-related proteins, but also unearthed several interesting aspects: how the workhorse proteins haul the cargo along microtubules (tiny molecular tracks inside the cells) and how they draw the energy to perform these tasks. But until recently scientists had little idea about what happens to the motors after they offload the cargo. Knowing the function ing of kinesins is important because it may open new avenues to understanding and fighting major diseases, including can cers and neuro degenerative disorders.
After studying one such motor protein called UNC104 in the roundworm Caenorhabditis elegans over five years, the scientists found that the vehicles that ferry the cargo are disposed of after their work is done. The job of UNC-104 is to bring neurotransmitters -chemicals that carry instructions from the brain to other parts of the body -to the synapse, a junction where orders are passed on from a neuron to another cell.
"It's quite like discarding the trucks after they have delivered vegetables to a mandi so that the traffic in the area remains smooth," says Koushika, the lead author. "If the neurons were to let these motors linger, it would be like getting caught in a traffic snarl -the more the trucks, the slower your exit," she explains. The NCBS researchers think the neurons do this because of their obsession with keeping it simple. "It's probably a strategy that pays big dividends," says Koushika.
The finding demonstrates proof of an alternative means of dealing with motors when they have ferried their packages. It may sound wasteful, but perhaps it is not, says Tole. "If the axon (long, slender projection of a nerve cell) they are in is very long, returning or reusing the motor may be costlier than getting rid of it." There are many neuro degenerative disorders we do not yet understand, and some of them could be because of neurons having lost some this necessary ruthlessness, says Koushika. Interestingly, it has been known for a long time that when cargo containing vital neurotransmitters lingers at synapses, neurological symptoms are precipitated.
This has been shown in animals. Similarly, it's known that it leads to much suffering in human families who share certain genetic defects. But until now, the possible causes of lingering cargo had not been identified. "We show that neurons have to deploy a clever biochemical mechanism to clear the decks of these motors. It is a system that could fail, leading to disease susceptibility," she says.
So, shooting the messenger at times does make sense, doesn't it?
Source: http://www.telegraphindia.com
