Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 182

currently an area of intense investigation. Given the critical roles of actin in
dendritic spine formation and function, there is significant potential for iso-
form specific roles during these processes ( Fukazawa et al., 2003 ; Honkura
et al., 2008 ; Hotulainen and Hoogenraad, 2010 ).
Dendritic spines and growth cones intriguingly share a large number
of similarities, with both largely dependent on the actin cytoskeleton and
its dynamics for the morphological changes required for proper function-
ing. Given the critical role for ZBP1 in growth cone function, and that it
also appears to be expressed in mature cultured neurons, it is not entirely
surprising that two studies have characterized apparent roles for ZBP1
in the formation and regulation of dendritic filopodia, the precursors of
spines. β-actin mRNA and ZBP1 were found to colocalize in small gran-
ules along the dendrites of cultured hippocampal neurons, and interestingly,
this colocalization could be enhanced following depolarization with KCl
( Tiruchinapalli et al., 2003 ). Similar to the study described above, knock-
down of ZBP1 resulted in a significant decrease in the dendritic localization
of β-actin mRNA and also reduced the density of dendritic filopodia under
both basal and BDNF stimulated conditions ( Eom et al., 2003 ). Overex-
pression of a full length β-actin construct with the zipcode sequence also
increased the density of dendritic filopodia as compared to expression of a
β-actin construct lacking the zipcode sequence ( Eom et al., 2003 ).
Collectively, these studies suggest that activity-regulated recruitment
of β-actin mRNA by ZBP1 may be an important mechanism initiating
dendritic spine morphogenesis, potentially by promoting the local transla-
tion and accumulation of β-actin. It is interesting to note, however, that
expression of epitope-tagged β- and γ-actin constructs were both strongly
localized to dendritic spines in the absence of the zipcode sequence ( Kaech
et al., 1997 ). Thus, as has been postulated by Welshhans et al. in growth
cones ( Welshhans and Bassell, 2011 ), ZBP1-mediated localization of β-actin
to dendritic filopodia and spines may only be required or functionally rel-
evant under certain conditions such as in response to synaptogenic signals
or synaptic stimulation. This, of course, is also dependent on ZBP1 being
expressed by mature neurons in vivo, which remains to be demonstrated.
Distinct functions for actin isoforms in mature dendritic spines, especially
as it relates to the encoding of memory and synaptic plasticity, represent
an incredibly exciting and completely unexplored aspect of actin isoform
function in neurons. Learning and memory are postulated to be encoded in
neural networks by either changes in the strength of synapses or the addi-
tion and/or elimination of existing ones ( Lamprecht and LeDoux, 2004 ).