Molecular Biology Faculty
Schultz Lab, 415
Molecular Architecture and Function of the Microtubule Cytoskeleton
We are interested in understanding how cells acquire their shape, position organelles, move materials, and segregate chromosomes during cell division. These features are essential for life and organized by the microtubule cytoskeleton, which resembles the skeletal system that supports our human body. Each cell type and shape requires a specific microtubule architecture. For instance, long and bundled microtubules make up the axonal extensions of a nerve cell that can reach up to 1 meter in length, whereas a spherical microtubule network renders a lymphocyte perfectly round. In contrast to the human skeleton, the microtubule cytoskeleton is also highly dynamic. Most cells regularly undergo cell division, during which the cell-type specific interphase microtubule network is completely disassembled and replaced by short and dynamic microtubules of the mitotic spindle to capture, align and then segregate chromosomes.
How is a specific microtubule architecture established at the molecular level?
Microtubules (red with growing tips in
green) grow off the wall of existing
microtubules, which is visualized by
total internal reflection (TIRF)
microscopy. This recently uncovered
mechanism, termed branching
microtubule nucleation, amplifies
microtubules while preserving their
polarity and is needed to assemble the
mitotic spindle of a dividing cell
(peTRY et al., cell 2013).Microtubules are cylindrical and dynamic polymers that consist of the protein tubulin. The biological function of the microtubule cytoskeleton relies on the precise arrangement of microtubules in the cell. To achieve this organization, microtubule associated proteins generate, sever, polymerize, shrink, bundle, anchor, or move microtubules. We want to understand these functionalities mechanistically and use this insight to explain how they ultimately result in the self-organization of the microtubule cytoskeleton.
We employ two complementary approaches that allow us to both look at structural detail of microtubule effectors and explain their function in the biological context. To study the mechanism by which microtubules are organized at a structural level, we use biophysical methods, electron microscopy and X-ray crystallography. To understand the dynamic assembly of the microtubule cytoskeleton, we combine biochemical and cell biological techniques along with advanced light microscopy methods.
Our goal is to identify and characterize new mechanisms that establish the cellular microtubule architecture. This will ultimately reveal how the microtubule cytoskeleton builds cellular structures to give cells their shape, position organelles, serve as tracks that move materials, generate force for movement, and segregate chromosomes.
Alfaro-Aco R, Petry S. (2015) Building the microtubule cytoskeleton piece by piece. J Biol Chem. [Epub ahead of print]
Petry S, Groen AC, Ishihara K, Mitchison TJ, Vale RD. (2013) Branching microtubule nucleation in Xenopus egg extract mediated by augmin and TPX2. Cell. 152: 768-77. Pubmed
Petry S, Vale RD. (2011) A new cap for kinetochore fibre minus ends. Nat Cell Biol. 13: 1389-91. Pubmed
Petry S, Pugieux C, Nedelec F, Vale RD. (2011) Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts. Proc Natl Acad Sci. 108: 14473-78. Pubmed
Uehara R, Nozawa RS, Tomioka A, Petry S,...Goshima G. (2008) The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells. Proc Natl Acad Sci. 106: 6998-7003. Pubmed
Weixlbaumer A, Jin H, Neubauer C,...Petry S,...Ramakrishnan V (2009) Insights into translational termination from the structure of RF2 bound to the ribosome. Science. 322: 953-56. Pubmed
Petry S, Weixlbaumer A, Ramakrishnan V. (2008) The termination of translation. Curr Opin Struct Biol. 18, 70-77. Pubmed
Weixlbaumer A, Petry S*, Dunham CM*, Selmer M*, Kelley AC, Ramakrishnan V. (2007) Crystal structure of the ribosome recycling factor bound to the ribosome. Nat Struct Mol Biol. 14: 733-37. Pubmed
Selmer M, Dunham CM, Murphy FV IV,...Petry S,...Ramakrishnan V. (2006) Structure of the 70S ribosome complexed with mRNA and tRNA. Science. 313: 1935-42. Pubmed
Petry S, Brodersen DE, Murphy FV IV,...Ramakrishnan V. (2005) Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon. Cell. 123: 1255-66. Pubmed