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Poster #1

Doublecortin is a structural marker for Taxol-induced expansion and compaction of the microtubule lattice


Sofia Cruz Tetlalmatzi, Alexandra Paquette, Muriel Sébastien, Adam Hendricks, Gary Brouhard

Department of Biology, McGill University. Department of Biological and Biomedical Engineering, McGill University

Taxol is a microtubule-stabilizing agent that is also an effective chemotherapeutic drug. Previous work has shown that high concentrations of Taxol expand the microtubule lattice. Taxol's lattice expansion effect influences the distribution of microtubule-associated proteins (MAPs), such as doublecortin (DCX), a MAP essential for brain development. DCX is composed of two globular microtubule binding domains, an N-terminal DC domain (DC-1) and a C-terminal DC domain (DC-2). These domains are sensitive to lattice curvature and protofilament number. The DC-1 domain recognizes the straight GDP-tubulin lattice, and the DC-2 domain recognizes the longitudinal curvature of GDP-Pi tubulin at microtubule tips. To investigate the effects of Taxol on the microtubule lattice, we have explored the dynamics of lattice expansion and compaction in vitro with the addition of Taxol to double GMPCPP-capped microtubules. The dynamic binding of DCX on the native microtubule lattice will function as a structural marker for expansion and curvature recognition, without interfering with protofilament number. Thus, by coupling in vivo and in vitro approaches of DCX binding on Taxol-bound microtubules, we aim to clarify how Taxol affects the microtubule lattice and demonstrate that MAPs can be used as markers of lattice structure.


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