2. INTRODUCTION
• Although microtubules possess the inherent ability to
form non-covalent polymers, a growing body of
evidence implicates the XMAP215/Dis1 family of TOG
domain-containing proteins as essential microtubule
polymerases. We are studying the Drosophila
homologue, Mini spindles (Msps), as a model for how
these proteins regulate microtubule dynamic
instability in vivo. Our data points to a mechanism in
which Msps is able to associate with microtubule plus
ends to promote microtubule assembly and convert to
a lattice-bound pool to spatially regulate microtubule
behavior in the cell periphery.
3. Mechanical crosslinking between
actin and microtubules
• Although the actin and microtubule networks are
frequently studied as independent systems, they
actually exhibit a high degree of crosstalk during
processes such as cell division, migration,
adhesion, and morphogenesis. This crosstalk can
manifest as signaling pathways that allow actin
and microtubules to locally influence each others
dynamics, or as a mechanical cross-linkage
between the two classes of cytoskeletal filaments
4. • Although a number of molecules have been shown to link
actin and microtubules, their cellular roles are unclear and
their regulation in living cells is poorly understood. We are
studying Drosophila Short stop (Shot) in order to
understand how actin-microtubule crosslinking is regulated
in the cell and to determine how it contributes to cell
motility and morphogenesis. We found that Shot is
required to maintain microtubule organization during
interphase and that its cross-linking activity is required to
resist deformative forces produced by microtubule motor
proteins. In the absence of Shot, kinesin and dynein deform
microtubules and cause them to exhibit exaggerated whip-like
movements.
5. Microtubule severing by AAA proteins
• Although the majority of microtubule growth and shrinkage occurs
from the plus end, microtubule architecture is also influenced by a
class of proteins that bind to the sides of microtubules and catalyze
the formation of breaks in the tubulin lattice. These proteins,
termed severing enzymes, play important roles in cell division, in
neuronal outgrowth, and in determining cell shape in plants.
Severing enzymes belong to the AAA ATPase superfamily - a
functionally diverse group of enzymes that function as protein
unfolding machines. Mutations in microtubule severing enzymes
have been implicated in human diseases that contribute to
neurodegeneration and various birth defects. Current projects in
the lab are addressing how severing enzymes contribute to
microtubule dynamics during cell migration and morphogenesis.