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Figure 3.5 Axonal filopodia emerge from actin patches in a manner correlating with
decreasing actin and PIP3 levels. (A) Actin patches and PIP3 microdomains attain their
maximal intensity at approximately the midpoint of their duration (arrow; Loudon et al.,
2006 ). Analysis of the time point during which filopodia emerge from patches, termed
the transition phase , indicates that filopodia emerge in large part after the midpoint of
patch development. The data are presented normalized to the duration of the individual
patches analyzed (e.g. if the filopodium emerged at 83% of the duration of the patch, it
was binned in the 81-90% bin). Activation of PI3K with a cell permeable peptide (PI3K-
pep) increases the duration of patches but does not change the probability that a patch
will give rise to a filopodium (Ketschek et al., 2010). The control for PI3Kpep in this data
set is the cell permeable portion of the peptide (Antp; top graph). Note that although
PI3Kpep increases the duration of patches, and PIP3 microdomains, it does not change
the relative timing of the emergence of filopodia from patches. (B) Speculative model
for the temporal regulation of axonal actin patch assembly and the emergence of filopo-
dia from patches based on the relative levels of PIP3/PIP2 in microdomains. The images
show the formation of a PIP3 microdomain (tracked using a GFP-PH domain of Akt) and
an actin patch (middle panel bottom). Elevating PIP3 levels in membrane microdomains
recruit molecules driving the Arp2/3-dependent formation of actin patches. The micro-
domain is denoted by the arrowheads in the panels, and reaches its peak intensity in the
middle panel. As PIP3 levels decline following their peak, PIP2 levels increase in micro-
domains. The increase in PIP2 levels recruits the molecular machinery driving the emer-
gence of a filopodium from the actin patch. Since the formation of a filopodium requires
multiple molecular systems, insufficient recruitment of any required component to the
microdomain may underlie the apparent stochastic nature of the emergence of filopo-
dia from patches (6-20% of actin patches give rise to filopodia depending on develop-
mental age of the neuron).
microdomains that have wide roles in cell signaling. A role for lipid rafts as
signaling platforms underlying the formation of filopodia was shown by
Scorticati et al. (2011) who report that filopodia induced by the integral
membrane glycoprotein M6a require M6a targeting to lipid rafts. Thus, lipid
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