How NSF/α-SNAP Disassembles the SNARE Complex in Intracellular Vesicular Trafficking

In 2013, Drs. James E. Rothman, Randy W. Schekman, and Thomas C. Südhof shared the Nobel Prize in Physiology or Medicine for their discoveries of molecular machineries for vesicle trafficking, a major transport system in cells for maintaining cellular processes. Vesicle traffic acts as a kind of "home-delivery service" in cells. Vesicles package and deliver materials such as proteins and hormones from one cell organelle to another. The vesicle releases its contents by fusing with the target organelle's membrane. One example of vesicle traffic is in neuronal communications, where neurotransmitters are released from a neuron. Some of the key proteins for vesicle traffic discovered by the Nobel Prize winners were N-ethylmaleimide-sensitive factor (NSF), alpha-soluble NSF attachment protein (α-SNAP), and soluble SNAP receptors (SNAREs). SNARE proteins are known as the minimal machinery for membrane fusion. To induce membrane fusion, the proteins combine to form a SNARE complex in a four-helix bundle, and NSF and α-SNAP disassemble the SNARE complex for reuse. In particular, NSF can bind an energy source molecule, ATP, and the ATP-bound NSF develops internal tension via cleavage of ATP. This process is used to exert great force on SNARE complexes, eventually pulling them apart. However, although about 30 years have passed since the Nobel Prize winners' actual discovery, how NSF/α-SNAP disassemble the SNARE complex has remained a mystery to scientists due to a lack the appropriate investigative methodology. Now, in article published in the March 27, 2015 issue of Science, a research team, led by Dr. Tae-Young Yoon of the Department of Physics at the Korea Advanced Institute of Science and Technology (KAIST) and Dr.
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