Anna Akhmanova, Cell Biology, Faculty of Science, Utrecht University, The
Netherlands
a.akhmanova@uu.nl
Lecture 1.
Regulation of microtubule dynamics
Various vital cellular processes, including the segregation of chromosomes,
directional cell migration and differentiation critically depend on the proper regulation
of microtubule dynamics. Microtubule polymerisation and depolymerization is tightly
controlled by a complex network of intracellular factors that are highly regulated in
space and time. Many of these regulators specifically associate with microtubule ends
where they can cooperate or antagonize each other. In this lecture, I will discuss the
molecular composition of microtubule end binding complexes and their effects on
microtubule dynamics.
Reading
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Desai, A. and T.J. Mitchison. Microtubule polymerization dynamics. Annu
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Howard, J. and A.A. Hyman. Microtubule polymerases and depolymerases.
Curr Opin Cell Biol, 2007. 19(1): p. 31-5.
van der Vaart, B., A. Akhmanova, and A. Straube. Regulation of microtubule
dynamic instability. Biochem Soc Trans, 2009. 37(Pt 5): p. 1007-13.
Akhmanova, A. and M.O. Steinmetz. Tracking the ends: a dynamic protein
network controls the fate of microtubule tips. Nat Rev Mol Cell Biol, 2008.
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Kumar, P. and T. Wittmann. +TIPs: SxIPping along microtubule ends.
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Su, X., R. Ohi, and D. Pellman. Move in for the kill: motile microtubule
regulators. Trends Cell Biol, 2012.
Lecture 2
A zoo at the tip: a dynamic protein network controls the fate of microtubule ends
Microtubule plus end tracking proteins (+TIPs) are a group of factors, which
specifically associate with the growing microtubule ends and regulate their dynamics
and interactions with various cellular structures. Recent studies showed that a
sequence motif Ser-any amino acid-Ile -Pro (SxIP) embedded in a basic, serine and
proline rich region can target a variety of proteins to microtubule ends by interacting
with the members of End Binding (EB) family. Since this motif is relatively short, it
can arise easily during evolution, and it is thus possible that multiple yet undiscovered
EB-dependent +TIPs are encoded in mammalian genomes. In this lecture, I will
describe the results of our searches for EB-binding +TIPs by combining proteomics
and bioinformatics approaches, and the known +TIP functions. I will also discuss an
example of how the geometry of microtubule network is controlled through
cooperation of +TIPs with a kinesin motor that regulates microtubule polymerisation.
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Bieling, P., L. Laan, H. Schek, E.L. Munteanu, L. Sandblad, M. Dogterom, D.
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system in vitro. Nature, 2007. 450(7172): p. 1100-5.
Maurer, S.P., F.J. Fourniol, G. Bohner, C.A. Moores, and T. Surrey. EBs
recognize a nucleotide-dependent structural cap at growing microtubule ends.
Cell, 2012. 149(2): p. 371-82.
Bieling, P., I.A. Telley, and T. Surrey. A minimal midzone protein module
controls formation and length of antiparallel microtubule overlaps. Cell,
2010. 142(3): p. 420-32.
Honnappa, S., S.M. Gouveia, A. Weisbrich, F.F. Damberger, N.S. Bhavesh,
H. Jawhari, I. Grigoriev, F.J. van Rijssel, R.M. Buey, A. Lawera, I. Jelesarov,
F.K. Winkler, K. Wuthrich, A. Akhmanova, and M.O. Steinmetz. An EB1binding motif acts as a microtubule tip localization signal. Cell, 2009. 138(2):
p. 366-76.
Montenegro Gouveia, S., K. Leslie, L.C. Kapitein, R.M. Buey, I. Grigoriev,
M. Wagenbach, I. Smal, E. Meijering, C.C. Hoogenraad, L. Wordeman, M.O.
Steinmetz, and A. Akhmanova. In Vitro Reconstitution of the Functional
Interplay between MCAK and EB3 at Microtubule Plus Ends. Curr Biol,
2010. 20(19): p. 1717-22.
Jiang, K., G. Toedt, S. Montenegro Gouveia, N.E. Davey, S. Hua, B. van der
Vaart, I. Grigoriev, J. Larsen, L.B. Pedersen, K. Bezstarosti, M. Lince-Faria, J.
Demmers, M.O. Steinmetz, T.J. Gibson, and A. Akhmanova. A Proteomewide Screen for Mammalian SxIP Motif-Containing Microtubule Plus-End
Tracking Proteins. Curr Biol, 2012.