Microtubule depolymerisers
Following DNA replication, distribution of the genome to daughter cells depends on the bipolar mitotic spindle. Microtubules are key structural elements of the spindle and their architecture and dynamics are controlled by teams of kinesin motors. These molecular motors bind to microtubules and use the energy of ATP to do work. Microtubules dynamics are essential for spindle function and in particular, control of microtubule length is a critical aspect of successful alignment and separation of sister chromatids. Lack of such control can cause chromosomal instability, which is linked to human cancer. However, the mechanisms by which microtubule length is regulated during cell division remain poorly understood.
We are studying the way in which kinesin motors control microtubule length through specialised depolymerisation activities. The importance of precise regulation of dynamics is emphasised by the two different families of depolymerising kinesins - kinesin-13s (also known as KinIs) and kinesin-8s - and we are interested in the molecular basis of their microtubule depolymerisation activities. Our work will provide fundamental insight into the similarities and differences of their depolymerisation mechanisms and ways in which these motors might be inhibited in dividing cells.
Francois-Xavier Chauviac is working on this project
Publications
Insight into the molecular mechanism of the multi-tasking kinesin-8 motor. Peters C, Brejc K, Belmont L, Bodey A, Lee Y, Yu M, Guo J, Sakowicz R, Hartman J, Moores CA (2010) EMBO J. 29:3437-3447
A new model for binding of kinesin 13 to curved microtubule protofilaments. Mulder AM, Glavis-Bloom A, Moores CA, Wagenbach M, Carragher B, Wordeman L, Milligan RA (2008) J Cell Biol. 2009 185:51-57
Visualisation of a kinesin-13 motor on microtubule end mimics. Moores CA, Milligan, RA (2008) J. Mol. Biol. 377:647-54
The role of the kinesin-13 neck in microtubule depolymerization. Moores CA, Cooper J, Wagenbach M, Ovechkina Y, Wordeman L, Milligan RA (2006) Cell Cycle 5:1812-5
Lucky 13-microtubule depolymerisation by kinesin-13 motors. Moores CA, Milligan RA (2006) J Cell Sci. 119:3905-13
Structure of a kinesin microtubule depolymerization machine. Shipley K, Hekmat-Nejad M, Turner J, Moores C, Anderson R, Milligan R, Sakowicz R, Fletterick R (2004) EMBO J. 23:1422-32.
Regulation of KinI kinesin ATPase activity by binding to the microtubule lattice. Moores CA, Hekmat-Nejad M, Sakowicz R, Milligan RA (2003) J. Cell Biol. 163:963-71
A mechanism for microtubule depolymerization by KinI kinesins. Moores CA, Yu M, Guo J, Beraud C, Sakowicz R, Milligan RA (2002) Mol Cell. 9:903-9
Collaborators
Professor Thomas Mayer (University of Konstanz, Germany)
