Moses V. Chao
Professor, Skirball Institute of Biomolecular Medicine, Molecular Neurobiology and Metabolic Signaling Program. Departments of Cell Biology, Physiology and Neuroscience, and Psychiatry.
Ph.D., 1980 University of California, Los Angeles
Neurotrophins, Signal Transduction, Neurodegeneration, Receptors
Skirball Institute of Biomolecular Medicine
540 First Avenue 5th floor, Lab 15-17
New York, N.Y. 10016
Office Tel: (212) 263-0721
Lab Tel: (212) 263-0722
Fax: (212) 263-8214
Tel: (212) 263-6354
Mechanisms of Growth Factor Receptor Action
Neurotrophic factors, such as NGF and BDNF, are not only required for neuronal growth, survival and differentiation in the nervous system, but also play a central role in learning and memory, anxiety, pain and psychiatric disorders. We are interested in the mechanism of action of neurotrophins, which use two different receptors, represented by the Trk tyrosine kinase receptor and the p75 receptor, the first member of the TNF receptor family. In particular, the adaptor proteins and enzymatic activities that are recruited to the Trk and p75 receptors to influence signaling, viral latency and neuronal plasticity are being investigated. Alterations in the levels of neurotrophins are highly influenced by neuronal activity and have been implicated in neurodegenerative disorders, such as Alzheimer’s disease, Rett syndrome and Huntington’s disease. Genetic and environmental factors that disrupt BDNF expression or signaling have also been associated with the development of a number of neuropsychiatric disorders, including major depression.
Ultimately, we are interested in what determines specificity in neurotrophic factor actions, in comparison to other growth factors. Difficulties in administering trophic factors have led to the consideration of using small molecule agonists to promote trophic functions, which may ultimately be clinically relevant. For instance, several ligands of G-protein coupled receptors can participate in transactivation of Trk receptors. Alterative ways of activating Trk receptors raise the possibility that small molecules may be used to elicit neurotrophic effects for the treatment of neurodegenerative diseases. Understanding the signaling mechanisms used by neurotrophins offer the opportunity to identify biochemical events and pathways that underlie cognitive function and complex neurological and psychiatric disorders at a molecular and cellular level.
- Lee, F.S. and Chao, M.V. (2001) Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc. Natl. Acad. Sci. USA 98, 3555-3560. PMID:11248116
- Yano, H., Ninan, I., Zhang, H., Milner, T.A., Arancio, O., Chao, M.V. (2006) BDNF-mediated neurotransmission relies upon a myosin VI motor complex. Nature Neuroscience 9, 1009-1018. PMID: 16819522
- Arevalo, J.C., Waite, J., Rajagopal, R., Beyna, M., Chen, Z-Y., Lee, F.S. and Chao, M.V. (2006) Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination. Neuron 50,549-559. PMID: 16701206
- Camarena, V., Kobayashi, M, Kim, J.Y., Roehm, P., Perez, R., Garner, J., Wilson, A.C., Mohr, I. and Chao, M.V. (2010) Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. Cell Host Microbe 8, 320-330. PMID: 20951966
- Mariga A, Glaser J, Mathias L, Xu D, Xiao M, Worley P, Ninan I, Chao MV (2015) Definition of a bidirectional activity-dependent pathway involving BDNF and Narp. Cell Reports. PMID: 26655895