Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 124

Heiman and Shaham (2010) proposed a role for tension generated by
filopodial dynamics in neuronal development. In this model, forces gener-
ated by filopodia following contact with postsynaptic partners are a com-
ponent of the mechanism that stabilizes filopodia. As noted previously in
Section 3.5 , intrafilopodial calcium fluxes can stabilize filopodia. Neurons
express mechanosensitive calcium channels and the activity of these chan-
nels impairs axon extension ( Jacques-Fricke et al., 2006 ). Thus, membrane
tension generated by the retraction of a filopodium that has attached to the
surface of a target cell may elicit calcium fluxes, which in turn contribute to
the stablization of filopodia. Calcium can control myosin II activity through
myosin light chain kinase, which is found in filopodia ( Kollins et al., 2009 ).
Interestingly, inhibition of myosin II impairs synaptogenesis, and increases
the proportion of dendritic filopodial protrusions relative to established
postsynaptic structures ( Ryu et al., 2006 ; Rex et al., 2010 ; Rubio et al.,
2011 ). While the mechanism underlying the effects of myosin II inhibition
on synaptogenesis remains to be fully elucidated, the forces generated by
myosin II contractility in filopodia may contribute to this process.
4. INITIATION, ELONGATION AND RETRACTION OF
NEURONAL FILOPODIA
4.1. Determination of the Sites of Filopodia Formation
As noted previously, neurons are highly polarized cells and the formation
of filopodia from the neuronal cell surface is similarly polarized. Bray and
Chapman (1985) provided the first detailed analysis of the sites of filopodia
formation at the axonal growth cone and along the axon shaft. A major
finding of this pioneering study was that filopodia formed with greatest
frequency, and retracted with the least frequency, at the leading edge of the
advancing growth cone, in alignment with the main axis of axon exten-
sion. The lateral sides of the growth cone exhibit decreased frequencies of
filopodial formation and increased retraction, and the rate of formation of
filopodia decreases greatly a few microns behind the neck of the growth
cone as the axon consolidates. The decrease in protrusive activity just proxi-
mal to the growth cone proper is a defining characteristic of the process of
axon consolidation, which gives rise to the axon shaft proper as the growth
cone advances (previously discussed in Section 2.2 ). Also, as discussed in
Section 3.3 , the establishment of asymmetries in the number of filopodia
at the growth often correlates with the redirection of axon extension by
guidance signals. The mechanisms that regulate the specific site of filopodial