Cytoskeletal Organization Laboratory

Anne Straube PhD - Group Leader

Daniel Roth
Binyam Mogessie, BSc
Ulrike Theisen, PhD

With immediate effect we have moved!

Our new contact details are:

Clinical Sciences Research Institute
Room B0.38
Clinical Sciences Research Institute
Warwick Medical School
University of Warwick
Coventry CV4 7AL

Tel: 024 7515 1168
Fax: 024 7652 8375
Email: A.Straube@warwick.ac.uk
http://www.mechanochemistry.org

For more information please visit our laboratory website

The cytoskeleton is important to keep the shape of the cell and serve as the tracks for transport processes inside the cell at the same time. Different from the human skeleton, the cytoskeleton is a flexible and dynamic arrangement of filaments, that can be quickly assembled into complex structures or disassembled, depending on the needs of the cell.

Our work concentrates on the role of microtubules, one of the three different types of filament that make up the cytoskeleton. Microtubules are hollow, flexible tubes that are build from tubulin subunits. Microtubules are usually nucleated and anchored at the centrosome, which is a small organelle close to the cell nucleus. The other end of microtubules often extends to the outer edges of the cell, making them a perfect track to transport gene products from the inner of the cell to the borders.

Microtubules play a vital role for many cellular processes such as the segregation of chromosomes, the transport of vesicles and organelles, locomotion of cells, as well as cell polarization and shape changes. In order to fulfil such specialized functions, microtubules need to be arranged into suitable arrays. Most animal cells contain a radial array of microtubules emanating from the centrosome. But nucleation of microtubule assembly is not restricted to the centrosome and occurs frequently independent of a major organizing centre, or MTOC. While microtubule distributions other than radial patterns are clearly of fundamental importance the detailed mechanisms underlying the generation of polarized microtubule arrays and the decisions governing radial versus other types of organization are poorly understood.

One system offering tractable insights into general mechanisms governing microtubule organization is that of differentiating muscle cells. During skeletal myogenic differentiation, myoblasts fuse to form multinucleated syncytia that eventually mature into myofibers. A critical early step in this process is the bipolar elongation of the previously isometric myoblasts. Parallel bundles of stable microtubules are formed that run along the length of the spindle-shaped cells. This process is very likely to require the anchoring of plus ends at the cell poles as well as extensive microtubule stabilization along their length in order to promote the growth of long microtubule polymers.

A major aim of our work is to investigate and describe the microtubule reorganization during myogenesis in detail and to identify and characterize proteins involved in the establishment and maintenance of the parallel microtubule array reaching the cell poles and thereby supporting cell elongation and myoblast fusion. We want to understand how the reorganization of the microtubule cytoskeleton is linked to morphological changes and to reveal mechanisms of how microtubule patterns are generated and adapted to fulfil specialized functions. Understanding these mechanisms will help us understand general processes that are essential for the modulation of cell morphology and function during cell differentiation.

What is the relevance of our work to cancer?

Loss of cell and tissue architecture is commonly associated with tumours, and contributes to the development of abnormal processes in cancer. Understanding in detail how cell structure and shape are generated will help us to identify the cellular functions that are deregulated in cancerous cells. That may lead to new ways to treat cancer.

Selected references:

Straube, A. and Merdes, A.  (2007)
EB3 regulates microtubule dynamics at the cell cortex and is required for myoblast elongation and fusion.
Current Biol., 17: 1318-1325.

Straube, A., Hause, G., Fink, G. and Steinberg, G. (2006).
Conventional kinesin mediates microtubule-microtubule interactions in vivo.
Mol. Biol. Cell., 17: 907-916.

Straube, A., Weber, I. and Steinberg, G. (2005).
A novel mechanism of nuclear envelope breakdown in a fungus: nuclear migration strips off the envelope.
EMBO J., 24 (9): 1674-1685.

Straube, A., Brill, M., Oakley, B.R., Horio, T. and Steinberg, G. (2003).
Microtubule organization requires cell cycle dependent nucleation at dispersed cytoplasmic sites, polar and perinuclear MTOCs in the plant pathogen Ustilago maydis.
Mol. Biol. Cell., 14: 642-657.

Wedlich-Söldner, R., Straube, A., Friedrich, M. and Steinberg, G. (2002).
A balance of Kif1A-like kinesin and dynein organizes early endosomes in the fungus Ustilago maydis.
EMBO J., 21 (12): 2946-2957.

Straube, A., Enard, W., Berner, A., Wedlich-Söldner, R., Kahmann, R. and Steinberg, G. (2001).
A split motor domain in a cytoplasmic dynein. EMBO J., 20 (18): 5091-5100.