When Less Is More For Brain Function

Researchers have found that a reduced supply of an enzyme called Rab4 can increase the density of synapses in the brains of fruit flies.

AsianScientist (Mar. 21, 2017) – Researchers at the Tata Institute of Fundamental Research have uncovered fresh insights into how synapses function. Their findings have been published in two papers in Cell Reports and the Federation of American Societies for Experimental Biology (FASEB).

Like the junctions in an electronic circuit between two semiconductors in an integrated computer chip, synapses in the brain constitute the logic of information flow. Simply put, neurons form functional synapses every time we learn something, and make us forget when they disappear.

Loss of synaptic functions in the human brain is at the root of many progressive neurodegenerative disorders such as Alzheimer’s disease. Although research has identified several factors that can potentially cause such disorders, the critical trigger is still elusive.

Neurons extend one of their projections into long axons which form synapses at the end. Sometimes—for example, in the case of the sciatic nerve—the distances could be as long as a meter. As all the proteins needed at the synapse are made near the nucleus that is far away from the synapse, neuronal cells employ a highly sophisticated transport system to maintain the supply of these proteins.

In the study published in Cell Reports, a team led by Professor Krishanu Ray found that the supply of a small GTP-hydrolysis enzyme called Rab4 could make a significant difference in the formation and organization of synapses. Interestingly, they showed that a reduced supply of the enzyme could increase the assembly of the synapse in the neuronal network, as well as corresponding brain functions of the fruit fly.

The study also showed that two different molecular locomotives of the kinesin class of proteins collaborate to ensure the appropriate supply of the Rab4 to the synapse.

In the study published in FASEB, Ray’s team found that a different pair of kinesin motors collaborate to deliver required quantities of acetylcholinesterase to the synapse.

Over-activation of acetylcholinesterase is implicated in accentuating the symptoms of Alzheimer’s disease. Incidentally, the loss of acetylcholinesterase activity suppresses neurite growth and synapse formation. Therefore, a neuron must maintain a calibrated balance of supplies towards synapses in order to maintain them.

Together, these results have opened another exciting possibility of using the fruit fly larvae to decipher underlying mechanisms of progressive neurodegenerative disorders such as Alzheimer’s disease.

The articles can be found at:
Dey et al. (2017) Anterograde Transport of Rab4-Associated Vesicles Regulates Synapse Organization in Drosophila.
Kulkarni et al. (2017) Heterotrimeric Kinesin-2, Together with Kinesin-1, Steers Vesicular Acetylcholinesterase Movements Toward the Synapse.


Source: Tata Institute of Fundamental Research; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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