INVESTIGADORES
KUNDA Patricia Elena
congresos y reuniones científicas
Título:
Moesin controls cortical rigidity, cell rounding and spindle morphogenesis during mitosis
Autor/es:
PATRICIA KUNDA; BUZZ BAUM
Reunión:
Conferencia; European Life Scientist Organization; 2008
Resumen:
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During mitosis, cells undergo a sequence of
morphological changes that include retraction of the cell margin and rounding,
followed by elongation at anaphase, invagination of the equatorial zone,
cleavage, and the respreading of the two daughter cells. Failure in any one of
these steps could lead to cell division and chromosomal segregation errors,
which have been implicated in several diseases including cancer.
We used a combination of RNAi, cell biology and
biochemical techniques to study changes in the structure and dynamics of the
actin cytoskeleton in cultured Drosophila cell lines. We show that Moesin becomes activated and cortically
localized following Slik-dependent phosphorylation at mitotic onset. This
cortical pool of active Moesin induces cortical stiffening and cell rounding,
and is sufficient to induce both processes in interphase cells, independently
of Myosin II. Strikingly, the soft mitotic cells that lack Moesin exhibit
profound defects in spindle morphogenesis and chromosome alignment, which can be
rescued by re-establishing cortical tension from the outside the cell. These
data show that the dynamic regulation of ERM protein activation and
localisation during mitosis controls the establishment of a stiff rounded
cortex at metaphase, and facilitates polar relaxation at anaphase. Moreover
changes in cortical rigidity are critical for the establishment and positioning
of the mitotic spindle, for chromosome alignment and for orderly spindle
elongation.
Using RNAi in Drosophila cell lines we screened for
kinases and phosphatases to identify those that control the mitotic
phosphorylation state of Moesin. We identified PP1-87B, which plays a key role
in the regulation of Moesin dephosphorylation, mitotic cell shape and passage
through mitosis. We further investigated in more detail
the functions of its regulatory subunits. Our latest
experiment will be presented together a model for the role of Moesin regulators
in controlling mitosis and possible implications for cancer progression.
