Karsenti
Group
General presentation
THE ROLE OF MICROTUBULES AND PHOSPHORYLATION
REACTIONS IN CELLULAR MORPHOGENESIS
Previous and current research Microtubules
are key players in the organization of cellular space. They are involved in
the positioning organelles during interphase, in the polarized transport of
vesicles in differentiated cells and in cellular morphogenesis in general. During
mitosis, their organization into a bipolar spindle allows the segregation of
chromosomes to the two daughter cells. In the past years we have been working
on the mechanism of mitotic spindle assembly that we took as an interesting
example of morphogenesis at the cellular level. Using frog egg extracts and
synthetic chromosomes made of magnetic beads coated with DNA we have shown that
a partly functional bipolar spindle can form around these artificial chromosomes
in the total absence of kinetochores, and centrosomes (see
movie). We believe that bipolarity results from the following basic principles:
i) mitotic chromatin introduces an asymmetry
in the mitotic cytoplasm that results in the preferential stabilization of microtubules
around chromosomes,
ii) once microtubules start to grow in random
orientation around the artificial chromosomes, motors present in the cytoplasm
and on chromosomes organize the microtubules into a bipolar array: this is a
self organization process
iii) the steady state length of the spindle
depends both on the regulated dynamics of spindle microtubules and on the movements
of microtubules inside the spindle which are powered by the activity of motors.
The preferential stabilization of microtubules around chromosomes seems to be
mediated by phosphorylation dephosphorylation reactions of Microtubule Associated
Proteins and of microtubule destabilizing proteins.
Future projects
Understand what is the nature of the effect
of chromatin on microtubule dynamics during mitosis, identify microtubule regulators
involved in spindle assembly and how phosphorylation reactions participate in
morphogenesis of the mitotic spindle. New cytoskeleton-dependent morphogenetic
systems will also be developed.
Goals
Understand the fundamental principles involved
in microtubule dependent morphogenetic events in the cell.
SELECTED PUBLICATIONS
Mitotic chromatin regulates phosphorylation
of Stathmin/OP18 [Andersen, S., Ashford, A. J., Tournebize, R., Gavet, O., Sobel,
A., Hyman, A., and Karsenti, E. (1997) Nature
389, 640-643]
Self organization of microtubules into bipolar
spindles around artificial chromosomes in Xenopus egg extracts [Heald, R., Tournebize,
R., Blank, T., Sandaltzopoulos, R., Becker, P., Hyman, A., and Karsenti, E.
(1996) Nature 382, 420-425]
Morphogenetic properties of microtubules and
mitotic spindle assembly [Hyman, A. A., and Karsenti, E. (1996) Cell
84, 401-410]