Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 127

Figure 3.4 Filopodia emerge from actin precursors structures (actin patches). (A) Exam-
ple of the emergence of an axonal filopodium from an actin patch precursors. The false
colored timelapse shows the dynamics of eYFP- β -actin in the axon of a cultured sen-
sory neuron. By 12 s, accumulation of actin is evident (arrow) in a patch along the axon,
and at 24 s, a filopodium begins to emerge from the patch (arrowhead). By 48 s, the
filopodium has extended further and the patch largely dissipated. (B) Imaging of eYFP-
β -actin along sensory axons in the living acutely explanted spinal cord of a chicken
embryo. Sensory neurons were transfected in vivo through in ovo electroporation (as
in Spillane et al., 2011 ). As shown in (A), an actin patch forms at 12 s and persists until
approximately 48 s. (C) Example of the emergence of a filopodium by a precursor accu-
mulation of actin at the growth cone of a neuron expressing eYFP- β -actin. The growth
cone, and the area focused upon in the subsequent panels, is shown in the leftmost
panel. An accumulation of actin is evident by 6 s (arrowhead), and a filopodium emerges
and extends between 18 and 24 s (arrows). For color version of this figure, the reader is
referred to the online version of this topic.
drives formation of filopodia at the growth cone and along the axon shaft
(i.e. both emerge from precursor actin-filament-based structures), but as
noted in Section 3.1 , there are also likely mechanistic differences.
Along axons, the sites of actin patch formation are determined by
localized microdomains of PIP3 signaling, which exhibit similar temporal
profiles as the patches ( Ketschek and Gallo, 2010 ). As PIP3 levels increase, so
does the actin content of the patch, and conversely as PIP3 levels decrease,
so does the actin content of the patch. PI3K signaling, leading to PIP3, is
both required and sufficient to elicit actin patch formation and the forma-
tion of axonal filopodia. These studies, thus, indicate that sites of filopodia
formation along axons arise in response to localized lipid-based signaling
events. WAVE proteins are activators of the Arp2/3 complex and can bind
to PIP3 ( Derivery and Gautreau, 2010 ). Overexpression of WAVE1 pro-
motes the formation of actin patches along sensory axons, but does not pro-
mote the emergence of filopodia from patches ( Spillane et al., 2012 ). The