Research Papers

Monitoring tau-tubulin interactions utilizing second harmonic generation in living neurons

[+] Author Affiliations
William H. Stoothoff, Brian J. Bacskai, Bradley T. Hyman

Massachusetts General Hospital-Harvard Medical School, Department of Neurology, Charlestown, Massachusetts 02129

J. Biomed. Opt. 13(6), 064039 (December 30, 2008). doi:10.1117/1.3050422
History: Received February 15, 2008; Revised September 04, 2008; Accepted October 14, 2008; Published December 30, 2008
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Tau is a microtubule associated protein that is localized to the axon in neurons. During pathological conditions, including frontotemporal dementia (FTD), a shift in tau isoforms occurs that leads to enhanced expression of a form of tau with four (rather than three) microtubule binding repeats; this has been postulated to alter microtubule structure. Second harmonic generation (SHG) is a technique that allows the visualization of intact microtubules in axons of living neurons without the need for labeling or fixing. We examined how the presence of exogenous tau influences SHG in living neurons. Our results show that the presence of tau significantly enhances SHG, specifically in neuronal axons, despite the presence of tau throughout the entire cell. Our data also suggest that the presence or absence of the fourth microtubule binding repeat does not significantly alter tau’s ability to enhance SHG. These results provide evidence that SHG is a useful, noninvasive tool to study tau-microtubule interactions in axons; further, it appears that tau overexpression, rather than specific isoforms, is the major contributor to tau-induced changes in axonal microtubule SHG signal.

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© 2008 Society of Photo-Optical Instrumentation Engineers

Citation

William H. Stoothoff ; Brian J. Bacskai and Bradley T. Hyman
"Monitoring tau-tubulin interactions utilizing second harmonic generation in living neurons", J. Biomed. Opt. 13(6), 064039 (December 30, 2008). ; http://dx.doi.org/10.1117/1.3050422


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