Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 109

visual system of Xenopus arise mainly from stable axon branches and not
from dynamic axonal filopodia ( P.P. Li et al., 2011 ). As discussed above,
axon branches arise from axonal filopodia, but axonal filopodia may be a
step removed from the mechanisms that give rise to presynaptic structures.
The mechanisms of the formation of axonal and dendritic filopodia and
branches are discussed in detail in the subsequent sections of this chapter.
The maturation of a dendritic filopodium into a spine is not discussed and
has been covered extensively elsewhere ( Chapleau et al., 2009 ).
3. MOLECULAR AND ULTRASTRUCTURAL
ORGANIZATION OF FILOPODIA
3.1. Filopodia: Identical Twins or Cousins?
The term filopodium is generally used to refer to a linear cellular protru-
sion that undergoes tip-mediated elongation. Filopodia are considered to
be structures supported by a bundle of actin filaments with the rapidly
polymerizing barbed ends pointed toward the tip of the elongating filopo-
dium. However, it is far from clear whether all cellular protrusions that fit
the above definition of a filopodium are generated by identical mechanisms.
Minimally, three basic events are required for the formation of a filopo-
dium: the nucleation of actin filaments, the elongation of actin filaments
through barbed end polymerization, and the orchestration of the filaments
into a polarized bundle. In cells, the nucleation, polymerization and orga-
nization of actin filaments can be regulated by multiple molecular systems.
For example, there are many actin filament nucleating system (e.g. formins,
Arp2/3, spire, cordon bleu; Firat-Karalar and Welch, 2011 ) and multiple
proteins that can organize filaments into bundles ( Winder, 2003 ). The gen-
eral appearance of filopodia can differ between cell types, different cells
in the same population, or even within the same cell. Figure 3.2 shows
examples of the appearance of actin filaments in filopodia from a variety of
cell types, as revealed by phalloidin labeling which specifically labels actin
filaments. Structures generally termed filopodia can consist of actin bundles
that form at the edge of the cellular perimeter and extend outward up
to 10 µm or more ( Fig. 3.2 A,C), or have tips that only slightly protrude
from the cellular perimeter but have long extended intracellular “ribs”
( Fig. 3.2 B,E). Thus, it is possible to imagine the formation of filopo-
dia through different, but not necessarily completely distinct, molecular
mechanisms, which, however, achieve the same end of generating a linear
actin-filament-based cellular protrusion.