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Scientists unravel mystery of brain cell growth
Date:8/8/2014

les. And most surprisingly, it binds those two molecules in different ways.

"Normally a receptor and a signal are like lock-and-key, they have evolved to bind each other and are highly specific and that's what we see in one netrin site," said Meijers. "But the second binding site is a very unusual one, which is not specific for DCC."

Not all of the second binding site connects directly to a receptor. Instead, in a large portion of the binding interface, it requires small molecules that act as middle-men. These intermediary molecules seem to have a preference for UNC5, so if the axon has both UNC5 and DCC receptors, netrin-1 will bind to one copy of UNC5 via those molecules and the other copy of DCC at the DCC-specific site. This triggers a cascade of events inside the cell that ultimately drives the axon away from the source of netrin-1, author Yan Zhang's lab at Peking University found. The researchers surmised that, if an axon has only DCC receptors, each netrin-1 molecule binds two DCC molecules, which results in the axon being attracted to netrin-1."By controlling whether or not UNC5 is present on its tip, an axon can switch from moving toward netrin to moving away from it, weaving through the brain to establish the right connection," said Zhang.

Knowing how neurons switch from being attracted to netrin to being repelled opens the door to devise ways of activating that switch in other cells that respond to netrin cues, too. For instance, many cancer cells produce netrin to attract growing blood vessels that bring them nourishment and allow the tumor to grow, so switching off that attraction could starve the tumor, or at least prevent it from growing.

On the other hand, when cancers metastasize they often stop being responsive to netrin. In fact, the DCC receptor was first identified as a marker for an aggressive form of colon cancer, and DCC stands for 'deleted in colorectal cancer'. Since colorectal cancer cells have no DC
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Contact: Teresa M Herbert
teresa_herbert@dfci.harvard.edu
617-632-5653
Dana-Farber Cancer Institute
Source:Eurekalert  

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