Physiological role found for Alzheimers protein
10 Jan 2018 by qwwqdccwwm.d qwwqdccwwm.d
A team working on neurodevelopment of axon growth have uncovered a role for TAU, a protein linked to neurological disorders, including Alzheimer’s disease.
Scientists from the The Scripps Research Institute in the US were studying the regulatory network behind the controlled termination of individual neuron growth – without which the efficient and accurate construction of a nervous system is in serious jeopardy.
At the heart of this process is a specialised structure on the end of each axon called a growth cone. Successful development depends on the growth cone stopping at the correct destination and when the axon is the correct length, a process known as axon termination.
“We know very little about the process of how axons actually stop growing in a living animal,” said team leader, Associate Professor Brock Grill. “What we found in our simple, but powerful model is that a signalling hub protein called RPM-1 is required to regulate the collapse of growth cones during axon termination.”
Grill’s team found that that while RPM-1 signalling destabilises axon microtubules, the microtubule stabiliser Tau potentially inhibits RPM -1, something that was previously unknown.
“People have very little knowledge about how TAU works under normal physiological conditions. Our results suggest that TAU inhibition of RPM-1 is necessary for proper axon development, and offers the first evidence that RPM-1 can be regulated in vivo in neurons.”
Published in the journal Development, the research has implications not only for the understanding of neurodevelopment but also for the development of neurological disorders. In mouse models, RPM-1 is an active force in axon degeneration and TAU has been linked to neurological disorders, including Alzheimer’s disease and frontal temporal dementia.
“You wouldn’t necessarily have thought Tau and RPM-1 would function this way,” said Grill. “That’s the power of genetics. Although we assessed the genetic relationship between Tau and RPM-1 in axon development, our results could have important implications for neurodegeneration.”
