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and drebrin-decorated filaments are less susceptible to the activity of actin
depolymerizing factor/cofilin. Thus, drebrin binding may serve to stabilize
actin filaments in the proximal filopodial shaft. In unpublished work, we
have found that shRNA-mediated depletion of drebrin in sensory neurons
results in an early termination of the extension of axonal filopodia. Filo-
podia begin to emerge from axonal actin patches, but usually do not attain
lengths >1-2 µm before retracting. Thus, the absence of drebrin may desta-
bilize actin filaments during the early phase of filopodial emergence, and
drebin may normally serve to stabilize the filaments close to the base of the
filopodium as its tip extends. In addition, drebrin binding to actin filaments
may also negatively regulate retrograde flow by decreasing myosin II inter-
actions with filaments, which is predicted to promote filopodial extension.
It is not currently clear what determines when a filopodial tip stops
elongating. One possibility is that sufficient actin monomer delivery by dif-
fusion fails at a certain distance from the base of the filopodium (
Zhuravlev
and Papoian, 2011
). Alternatively, additional molecular machinery required
for maintaining the tip elongating may not be effectively delivered in a
timely manner beyond a certain length. It is also possible that the tip com-
plex machinery thought to drive elongation of the filopodial tip may have
a “clock,” which allows the relevant signaling/biochemical mechanisms to
shut down after a certain time period (e.g. if necessary proteins are post-
translationally modified as a function of time and the relevant demodifying
system, e.g. a phosphatase, is not available at the filopodial tip, or vice versa).
Neuronal filopodia, by virtue of their dynamics and lengths, will likely be
crucial in addressing these intriguing questions.
4.4. Retraction and Stabilization of Filopodia
Filopodia are dynamic in vitro and in vivo, undergoing initiation extension
and retraction. The regulated stabilization of filopodia is, however, funda-
mental to aspects of neuronal development. The heterogeneous stabilization
of growth cone filopodia is a component of growth cone response to attrac-
tant and repellent guidance signals. In a single filopodium-mediated growth
cone turning toward an attractant signal (e.g. neurotrophins bound to beads
or contact with the surface of a guidepost cell; see Section
2.2
), the stabiliza-
tion of the contacting filopodium is an early event in turning. In these cases,
the stabilization of the filopodium correlates with the accumulation of actin
filaments within the filopodium and the entry/capture of microtubules
(
Sabry et al., 1991
;
O'Connor and Bentley, 1993
;
Bentley and O'Connor,
1994
; see Section
5.2
). In contrast, filopodia stabilization is also involved in
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