Structure and function of the neuronal cytoskeleton and its role in neurodegenerative diseases
Tau protein is a microtubule-associated protein that is critical for neuronal development. Our laboratory has been elucidating new functions for tau beyond its ability to promote microtubule assembly and stability. We have found that tau can be a membrane-associated protein with putative roles in signal transduction. In particular, we have discovered an interaction between tau and src family non-receptor tyrosine kinases. We are currently investigating the functional implications of this interaction in neuronal and non-neuronal cells. For example, the interaction may affect the spatial localization of tau, the activity of the tyrosine kinase, or the phosphorylation of tau. We are also investigating other new interactions of tau. In our studies, we use a combination of cell biological, molecular biological, and biochemical tools and assays.
Tau is also a prominent component of the neurofibrillary tangles of Alzheimer's disease. In addition, mutations in the tau gene cause other age-related neurodegenerative diseases such as frontotemporal dementia. The mechanisms underlying the formation of abnormal tau lesions in Alzheimer's disease and other dementias and the mechanisms that cause neuronal cell death in these age-related diseases are unknown. We are testing the hypothesis that tau's interactions with proteins other than microtubules, have a role in the neurodegenerative process.
C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death.
Kanmert D, Cantlon A, Muratore CR, Jin M, O'Malley TT, Lee G, Young-Pearse TL, Selkoe DJ, Walsh DM.
J Neurosci. 2015 Jul 29;35(30):10851-65. doi: 10.1523/JNEUROSCI.0387-15.2015
Tau in MAPK activation.
Leugers CJ, Koh JY, Hong W, Lee G.
Front Neurol. 2013 Oct 17;4:161. doi: 10.3389/fneur.2013.00161. eCollection 2013.
Tau and tauopathies.
Lee G, Leugers CJ.
Prog Mol Biol Transl Sci. 2012;107:263-93. doi: 10.1016/B978-0-12-385883-2.00004-7. Review.
Tubulin-independent tau in Alzheimer's disease and cancer: implications for disease pathogenesis and treatment.
Souter S, Lee G.
Curr Alzheimer Res. 2010 Dec;7(8):697-707. Review.
Tyrosine phosphorylation of tau accompanies disease progression in transgenic mouse models of tauopathy.
Bhaskar K, Hobbs GA, Yen SH, Lee G.
Neuropathol Appl Neurobiol. 2010 Oct;36(6):462-77. doi: 10.1111/j.1365-2990.2010.01103.x.
Tau potentiates nerve growth factor-induced mitogen-activated protein kinase signaling and neurite initiation without a requirement for microtubule binding.
Leugers CJ, Lee G.
J Biol Chem. 2010 Jun 18;285(25):19125-34. doi: 10.1074/jbc.M110.105387. Epub 2010 Apr 7.