Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 134

activity, which in turn suppresses the emergence of filopodia from actin
patch precursors ( Loudon et al., 2006 ). A recent report found that p120
catenin is required for the formation of filopodia along the axons of cultured
spinal neurons ( Chen et al., in press ). p120 catenin can regulate Rho-family
GTPases and a truncated catenin not able to do so acts a dominant nega-
tive resulting in suppression of filopodia formation from along the axons.
The effects of catenin are likely to be due to regulation of RhoA, which
suppresses the formation of axonal filopodia ( Chen et al., in press ). Sema-
phorin 3A causes growth cone collapse and shuts down production of filo-
podia and lamellipodia in a RhoA- and RhoA-kinase-dependent manner,
and also blocks the formation of axonal filopodia through a RhoA-kinase-
dependent inhibition of the formation of axonal actin patches ( Gallo, 2006 ).
There is much crosstalk between these GTPases and a full story in neurons
has not yet emerged. However, it seems likely that different GTPases may
be able to tap into the mechanism of filopodia formation in an intra- and
extracellular context-dependent manner.
4.3. Polymerization, Deploymerization and Retrograde Flow
of Actin Filaments in Filopodia
Depending on the extracellular context and neuron type in vitro, the tips of
neuronal filopodia extend and retract with rates in the 0.1-0.2 µm/s range
( Gehler et al., 2004 ). In vivo filopodial dynamics are attenuated, likely due
to being in a three-dimensional environment with cell-to-cell membrane
interactions available on all sides of the filopodium, and having to maneu-
ver through a cellular environment. However, in vitro and in vivo filopodia
exhibit a range of behaviors characterized by bending at hinge points, giv-
ing rise to new filopodia from the shaft of existing filopodia, and lateral
swinging motions of the whole filopodium ( Portera-Cailliau et al., 2003 ;
Fig. 3.1 ). During the life cycle of an individual growth cone filopodium,
the tip can undergo alternating bouts of elongation and retraction, suggest-
ing temporary imbalances in the regulation of the mechanisms that control
tip extension and retraction. In growth cone lamellipodia, actin filaments
polymerize mostly with their barbed ends directed toward the leading edge,
and then subsequently undergo retrograde flow toward the central domain
in a myosin II and filament polymerization-dependent manner ( Lin et al.,
1996 ). Similarly, within individual growth cone filopodia, actin polym-
erization and retrograde flow determine the behavior of the filopodium
( Mallavarapu and Mitchison, 1999 ). Even within a single filopodium, the rate
of polymerization and retrograde flow can be regulated during its lifecycle,