Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 138

These data suggest that localized regulation of gelsolin activity in filopodia
may contribute to the stabilization of filopodia during responses to guid-
ance signals. Actin depolymerizing factor and cofilin, similar to gelsolin,
also sever actin filaments. Overexpression of these molecules resulted in an
increased number of filopodia at growth cones, but a decreased number of
filopodia along the distal axon ( Meberg and Bamburg, 2000 ). Although this
study did not address the dynamics of filopodia, it suggests that actin depo-
lymerizing factor and cofilin may also have a role in regulating filopodial
stability, and if so, differently at the growth cone and along the axon.
5. FILOPODIA: LINKING THE ACTIN AND
MICROTUBULE CYTOSKELETON
5.1. Concerted Dynamics and Organization of the
Neuronal Microtubule and Actin Cytoskeleton
Although there is no molecular similarity between actin filaments and
microtubules, and the two cytoskeletal systems do not interact directly, it
has become clear that indirect mechanisms exist in neurons linking the two
systems both at the mechanical and molecular level. Original insights indi-
cating that microtubules could regulate aspects of actin cytoskeletal dynam-
ics came from studies of the effects of microtubule disrupting agents on
the motility and dynamics of nonneuronal cells ( Bershadsky et al., 1991 ;
Kaverina and Straube, 2011 ). Similarly, attenuating microtubule tip dynam-
ics, depolymerizing microtubules or causing aberrant microtubule polym-
erization have all been shown to affect actin-filament-based protrusion in
neurons ( Bray et al., 1978 ; Tanaka and Kirschner, 1991 ; Gallo, 1998 ). Con-
versely, actin filaments and myosin II activity regulate the distribution of
microtubule tips in growth cones ( Schaefer et al., 2002 ; Burnette et al.,
2007 ; Ketschek et al., 2007 ). Recent advances have begun to shed light on
the molecular mechanisms that link microtubules and actin filaments. The
following sections address how the actin and microtubule cystoskeleton is
integrated during growth cone guidance mediated by filopodia and axon
collateral branching.
5.2. Actin and Microtubules in Filopodia-Mediated Growth
Cone Guidance
Growth cone guidance in response to extracellular signals requires both
actin filaments and microtubules. Actin-filament-based structures (filopodia
and/or lamellipodia) are generally considered to be required for the