Скачать или смотреть Physiology Shorts: Investigating phosphorylation in two discrete tau domains

In this Physiology Shorts video, Professor Dezhi Liao (University of Minnesota Medical School, USA) talks about his recent publication in The Journal of Physiology investigating phosphorylation in two discrete tau domains.

Read the paper in The Journal of Physiology:
Phosphorylation in two discrete tau domains regulates a stepwise process leading to postsynaptic dysfunction.
Peter J. Teravskis, Breeta R. Oxnard, Eric C. Miller, Lisa Kemper, Karen H. Ashe, Dezhi Liao
Volume 599(9), pp. 2483-2498
https://physoc.onlinelibrary.wiley.co...

Transcript:
Hello, I am Dezhi Liao, a Professor in the Department of Neuroscience at the University of Minnesota.

We are studying the cellular mechanism underlying Alzheimer’s dementia, frontotemporal dementia, and chronic traumatic encephalopathy. All these diseases contain neurofibrillary tangles in the brain. The major component of neurofibrillary tangles is tau. However, we still do not know how it causes dementia.

We study dendritic spines because we know that, definitely, dendritic spines are important for deficits in learning and memory.

We made mutations in three phosphorylation domains in the tau. In the A domain, B domain and C domain in the tau. We transfect GFP-tagged mutant tau to neurons in order to regulate tau activity. At the same time, we co-transfect DsRed to label the morphology of neuron. At the same time, we record electrophysiological responses of the neuron in order to detect functional deficits.

We found that, in order for tau to cause synaptic deficits, it will take two steps. In Step 1, phosphorylation of the C domain will drive tau to dendritic spines. In Step 2, phosphorylation of the B domain will lead to subsequent synaptic deficits.

Our findings are important mechanistically because we are providing a novel cellular mechanism for how tau phosphorylation causes synaptic deficits, leading to dementia. Our study is also important translationally because strategies can be developed to block the phosphorylation of the B or C domain to treat neurodegenerative diseases.