Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 114

that all filopodia will contain all listed proteins, but serves as a template for
the general molecular organization of neuronal filopodia. For the purpose
of this discussion, the filopodium is broken down into the following four
subdomains: (i) the base of the filopodium, (ii) the proximal segment of
the filopodium, (iii) the remainder of the distal filopodial shaft and (iv)
the filopodial tip. Molecules representative of adhesion mechanisms, signal
transduction apparatus, vesicle traffic, and regulation of actin filaments have
all been localized within filopodia.
The base of the filopodium is the site where the filopodium originally
formed. The mechanisms of the initiation of filopodia are discussed in
Section 4.1 . Analysis of the organization of actin filaments at the base of
established neuronal filopodia using electron microscopic techniques has
revealed that actin filaments undergo convergence into the filopodia shaft
( Korobova and Svitkina, 2008 , 2010 ; Spillane et al., 2011 ), consistent with
the convergent elongation model ( Svitkina et al., 2003 ). At the growth cone,
the role of Arp2/3 in initiation of filopodia differs between cell types or in
an extracellular context-dependent manner ( Strasser et al., 2004 ; Korobova
and Svitkina, 2008 ; Norris et al., 2009 ). In contrast, along the axon shaft,
Arp2/3 is required for the formation of filopodia and collateral branches
( Strasser et al., 2004 ; Spillane et al., 2011 ). In the case of axonal filopodia,
regulators of the Arp2/3 complex have also been localized to the base of
filopodia (e.g. WAVE1/3, cortactin; Spillane et al., 2011 ; Hu et al., 2012 ).
Myosin II also targets to the base of filopodia, and inhibition of myosin II
increases the number of filopodia both at the growth cone and along the
axon shaft ( Gehler et al., 2004 ; Loudon et al., 2006 ). Septins are a family
of heterooligomeric proteins with various cellular functions, often linked
to the regulation of the cytoskeleton ( Mostowy and Cossart, 2012 ). Septin
6 binds actin filaments, preferentially at Arp2/3-mediated branches, and
is found at the base of axonal and dendritic filopodia and in both cases,
it is involved in the formation of branches ( Cho et al., 2011 ; Hu et al.,
2012 ). The base of growth cone filopodia also represents a site of substratum
attachment and contains an ultrastructure termed the basal ring ( Steketee
et al., 2001 ). Unfortunately, little is known about the molecular compo-
sition of this intriguing structure. However, the Rac1 GTPase has been
localized to rings (personal communication by Dr K. Tosney, University of
Miami). Rac1 localizes to the actin patch precursors to the formation of
axonal filopodia, and inhibition of Rac1 function decreases the number of
filopodia both along the axon and at the growth cones of sensory neurons
( Spillane et al., 2012 ).