Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 112

protein fascin, which is otherwise found in filopodia, and due to its oth-
erwise ubiquitous localization to filopodia, is even used as a filopodial
“marker” ( Dent et al., 2007 ).
Consideration of the studies discussed above suggests that filopodia may
not be a unitary biological phenomenon, but rather as a final functional out-
come that can be attained through multiple molecular mechanisms operating
under the umbrella of a few general organization/mechanistic schemes.
Indeed, recent studies of neuronal filopodia demonstrate that there are multiple
molecular mechanisms that can orchestrate the formation of filopodia even in
the same cell (Sections 2.1 and 3.2 ). Furthermore, as noted in a recent review
( Michelot and Drubin, 2011 ), the nucleation mechanism of filaments can alter
their physical properties and also the set of molecules that associate with fila-
ments. As different filopodia may be derived from actin filaments nucleated
by different nucleation mechanisms, which will impart different properties to
the filaments, this may reflect the existence of functional subtypes of filopodia
(e.g. axonal filopodia versus growth cone filopodia versus dendritic filopodia).
Thus, it may be cautious to consider that although as a collective filopodia
appear as closely related twins based on their phenomenology, they may be
more akin to cousins belonging to a general family reflective of a cytoskeletal
organizational scheme that can be tapped into through multiple molecular
mechanisms, perhaps leading to functional differences.
3.2. Subfilopodial Localization of Proteins
The molecular composition of filopodia exhibits a striking degree of com-
partmentalization. At face value, the filopodium can be considered to be a
“simple rod” made of parallel aligned actin filaments. However, structural
and regulatory molecules are not uniformly distributed along this decep-
tively simple structure. This section addresses the molecular organization of
neuronal filopodia.
As noted in Section 3.1 , some filopodial filament bundles emerge directly
from the cell's edge, while other exhibit “ribs” that localize many microns
into the cytoplasm before giving rise to a usually short filopodial protru-
sion from the cell's edge. This section focuses on the former as they are the
most commonly observed type and found in the growth cones of actively
extending axons and axonal filopodia. Figure 3 .3A shows an overview of
the localization of a variety of molecules within neuronal filopodia, and a
few examples of selected proteins (panels B and C). The list in this figure
was generated based on reports of the localization of these proteins in either
axonal growth cone or shaft filopodia. The list is not intended to imply