New Mechanism for NF1 Brain Cell Growth Control Identified
Brain tumors develop in one-fifth of children with NF1. While these tumors are classified as benign, most occur in the optic nerve where they can cause vision loss. Currently, children are treated with standard chemotherapy with positive outcomes in half of those who receive these treatments. In order to discover therapies targeted specifically to NF1-brain tumors, several groups have employed Nf1 mutant mice.
Previous studies in the laboratory of Dr. David H. Gutmann, the Donald O. Schnuck Family Professor and Director of the Washington University NF Center have shown that optic glioma growth in Nf1 mutant mice is controlled by a protein called the mechanistic target of rapamycin (mTOR).
While many studies have defined how the mTOR protein complex functions in skin cells and cancer cell lines, far less is known about mTOR regulation in the brain.
Exciting new studies spearheaded by Dr. Laura Smithson, a senior postdoctoral fellow in Dr. Gutmann’s laboratory, have revealed that the composition of the mTOR complex is unique in brain cells (astrocytes). Leveraging proteomic, genetic, and pharmacological methods, Dr. Smithson identified a new protein, called GIT1, in the mTOR complex of brain cells, and showed that this protein is essential for mTOR complex control of astrocyte survival.
In addition, she found that the GIT1/mTOR complex represents a novel mTOR complex, as well as a new therapeutic target for brain tumor therapies.
Smithson LJ, Gutmann DH. Proteomic analysis reveals GIT1 as a novel mTOR complex component critical for mediating astrocyte survival. Genes Dev. 2016 Jun 15;30(12):1383-8. doi: 10.1101/gad.279661.116.