2008 Brain Star Award Recipient - Christopher Tsang
Recipient
Christopher Tsang - Biosketch
PhD
University of Toronto
Article
Superfluous role of mammalian septins 3 and 5 in neuronal development and synaptic transmission. Tsang CW, Fedchyshyn M, Harrison J, Xie H, Xue J, Robinson PJ, Wang LY, Trimble WS. Mol Cell Biol. Sep 22 2008 [Epub ahead of print]
Significance of the paper
Septins are a family of filament-forming proteins that were originally discovered for their importance in cell division. Surprisingly, septins were also discovered in brain tissue, which is comprised of neurons, which do not divide. Deciphering the role of neuronal septins is important because of their links to several neurological diseases. They are found within neurofibrillary tangles in brains affected by Alzheimer's disease, within Lewy bodies in brains affected by Parkinson's disease, and in disproportionate levels in brains affected by schizophrenia.
Previously, we published a paper [Xue, Tsang et al. (2004), j. Neurochemistry 91(3):579] showing that Septin 3 is exclusively made in neurons in a developmentally-regulated manner. Within presynaptic terminals, Septin 3 associates with synaptic vesicles and membranes. This study was critical in laying the ground work for the present study, which examines Septin 3 function in the CNS using targeted gene disruption in mice. Although the loss of Septin 3 was expected to impact synaptic transmission, we unexpectedly found very little deficit in brain function even when Septin 5 was disrupted too.
The anatomy, biochemistry and physiology in this paper have set the highest standards to date by which synaptic transmission should be assessed in septin knockout mice. This study clearly demonstrates that neuronal septins are complex and has paved the way for more refined measurements in combination knockout mice. Given the link of septins to several neurophathies, it should be a very promising area of study. This body of work was published in Molecular and Cell Biology because it has the highest impact for work on mouse mutants with undetected or complex phenotypes.