AXIN1 - a possible conductor of the transition between muscle growth and loss
mTORC1 and AMPK are two key intracellular signal proteins that control growth and degradation/reuse of the cell, respectively. A coordinated and reciprocal regulation of these proteins (switching one off when the other is active) is critical to the function of cells and has recently been proposed to be coordinated by the protein AXIN1. This project investigates the importance of AXIN1 in muscle using transgenic mice that specifically lack AXIN1.
Activation of mTORC1 triggers an anabolic (growth) response in muscle while activation of AMPK triggers a catabolic (breakdown) response. In many cases, there is known to be a reciprocal regulation of mTORC1 and AMPK in order to prevent these opposing proteins from being activated simultaneously and thereby creating molecular tug-of-war.
AXIN1 is part of a complex shown in cells to activate AMPK and inhibit mTORC1. However, the role of AXIN1 has not directly investigated in muscle. Our working hypothesis is that mice without AXIN1 will exhibit a reduced ability to activate AMPK and a constant activation of mTORC1.
A better understanding of how the mTORC1 and AMPK activity is coordinated can lead to new drugs that counteract muscle loss but also affect other conditions where these proteins are believed to play a role, including cancer and cellular aging.
Novo Nordisk Foundation and the Chinese Scholarship Council.