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model organism. Next, I had to track Kinesin moving in a neuron of a worm. That was made possible by green fluorescent proteins (GFPs). Explained in simple terms, these proteins worked like ‘glow in the dark’ objects. Some of the scientists in our community had already tried attaching GFP to motors. However, they realized that attaching GFP with Kinesin might hamper its function, so they proceeded with putting GFP on the vesicles. And, that worked beautifully! Thanks to fellow scientists, I could now see the vesicle being carried by Kinesin moving within the neuron of a living worm under a microscope! What next? I sat day and night just watching those vesicles move in the neuron and observing their behaviour.
It was exciting to see Kinesin carry all the vesicles (from here on referred to as cargoes) in real time, which gave me some interesting insights as to how it might be navigating complex paths. The first thing that struck was that in a neuron,
there were a lot of cargoes
that were not moving at all. In
a neuron where the supply of
raw materials was so important,
it was surprising to see that
almost half the population of
cargo stuck for several minutes.
On further investigation, I
found that the stuck cargoes
were predominantly present
at the following locations: at
the bush like actin networks,
at another vesicle that had
stopped moving somewhere in
the middle of the road, and at
a vesicle already stalled at an
actin bush. From these data,
a series of events that might
inside the neuron could be imagined. A moving cargo first encountered the dense actin bush and stopped. This cargo stalled at an actin bush would then act as an even
Dr Parul Sood || 27
more effective block to incoming cargoes. These events closely resembled the traffic jams that we observed on the roads every day when we stepped out. However, unlike traffic jams on the road, which were regulated and controlled by the traffic police, there was no such regulation in the neurons. Rather these jams in the brain purely arose due to physical blocks preventing the cargo from moving, and as soon as the physical block was removed, the cargoes mobilized too. These traffic jams in the neurons were, thus, not permanent.
In addition to this, I found that 8 out of 10 cargoes stopped at these traffic jams. The cargoes stopping at such a rate at traffic jams would eventually result in almost negligible flow in the neuron. However, the neuron managed to maintain the flow of vesicles despite the presence of these roadblocks. Each time, say, eight cargoes halted at a roadblock; six to seven vesicles managed to sneak out from the
same roadblock and continued on their journey to the synapse, very similar to motorcyclists on Indian roads. Another way by which cargoes avoided jams was by changing their direction of motion and running away from such locations only to continue on paths that were likely not blocked. Smart, right! For me, the amazing thing was that the complex decisions we made while navigating traffic on the road were seamlessly made by a billion time smaller molecules in the neurons. Impressive! But wait, there was more. Since traffic jams could be avoided,
neurons utilized the cargoes stopped in traffic jams as stores of raw materials. These stores could cater to the high demands of raw materials at the synapse in situations where the brain was required to do extra work. To
Vesicles were carried in both directions; Kinesin carried them from the cell body to the synapse, and Dynein carried them from the synapse to the cell body. Therefore, both Kinesin and Dynein faced these blocks on their way. This problem that hundreds of Kinesins and Dyneins were facing then became my research problem!
be occurring