Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 108

of postsynaptic structures and the maturation of the filopodium into a syn-
apse bearing branchlet ( Heiman and Shaham, 2010 ). One of the hallmark
molecules of a functional postsynaptic structure is the postsynaptic density
protein PSD-95, which acts as a scaffold for many other synaptic compo-
nents. Brain derived neurotrophic factor (BDNF) is an important regula-
tor of dendritic development ( Horch, 2004 ). Accumulation of PSD-95 in
dendritic filopodia is regulated by BDNF signaling. Interestingly, BDNF
promotes the targeting of PSD-95 through regulation of the entry of den-
dritic microtubule tips into maturing dendritic filopodia ( Hu et al., 2011 ).
Cypin is an additional link between dendritic filopodia, PSD-95 and the
regulation of microtubules during maturation of the filopodium into a
branch ( Firestein et al., 1999 ). Cypin is a guanine deaminase that binds
PSD-95 and promotes microtubule polymerization and dendritic branch-
ing ( Georges et al., 2008 ). Furthermore, PSD-95 also interacts with micro-
tubule end-binding protein 3 (EB3) and adenomatous polyposis coli (APC)
and these interactions have been suggested to inhibit and promote dendrite
branching, respectively ( Georges et al., 2008 ). These studies link regulation
of microtubule entry into dendritic filopodia and the process of dendritic
branching. However, a complete analysis of the cytoskeletal mechanisms of
dendritic branching is lacking.
2.4. Formation of Synaptic Structures
Functional chemical synapses represent contacts between the membranes of
the pre- and postsynaptic neurons. The mature chemical synapse consists of
a postsynaptic side and a presynaptic active zone, and a synaptic cleft sepa-
rating the two. In most cases, both structures are in the order of one to a
few micrometers. Neurotransmitters are released through the exocytosis of
vesicles, present in the presynaptic active zone, into the synaptic cleft where
they bind receptors and activate signaling pathways in the postsynaptic but-
ton. The formation of dendritic filopodia is well established as one for the
first steps in the process of synaptogenesis ( Menna et al., 2011 ). Following
contact with the presynaptic neurons, the dendritic filopodia maturate into
structures termed spines . Similarly, the filopodia of axons may serve as the
presynaptic structures that mature into active zones. Consistent with this
notion, highly dynamic axonal filopodia/branch protrusions contain synap-
tic vesicle release machinery ( Pinches and Cline, 1998 ). However, a recent
detailed live imaging and electron microscopy correlative study, while
confirming that dendritic filopodia are precursors to postsynaptic struc-
tures, has revealed that functional presynaptic structures in the developing