Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 183

Long-term potentiation (LTP) is one means of increasing the strength of
existing synapses and is currently believed to be a molecular mechanism
underlying the encoding of memory. In experiments with cultured neu-
rons and in vivo, stimulation of neurons leading to the induction of LTP
is strictly dependent upon an increase in actin polymerization within
spines, occurring within minutes of stimulation and generally leading to
an increase in spine volume and insertion of neurotransmitter receptors
( Fukazawa et al., 2003 ; Honkura et al., 2008 ; Matsuzaki et al., 2004 ; Oka-
moto et al., 2004 ). High magnitude but transient intracellular Ca 2+ signals are
also critical for the induction of LTP in dendritic spines ( Oertner and Matus,
2005 ). While the functions of this Ca 2+ signal most certainly affect actin
dynamics indirectly through the modulation of actin-binding proteins, it is
also tempting to speculate that this could more directly affect actin polym-
erization (specifically β-actin) by elevating the levels of Ca 2+ bound β- and
γ-actin. Intriguingly, multiple populations of actin with distinct localizations
and turnover rates have now been observed in dendritic spines at rest and
in those stimulated by glutamate to mimic synaptic transmission ( Honkura
et al., 2008 ). It is thus tempting to speculate that microgradients of Ca 2+ adja-
cent to channels within the plasma membrane may lead to the manifestation
of the distinct polymerization kinetics of Ca 2+ bound β- and γ-actin, adding
another layer to the complexity of postsynaptic actin regulation. Future stud-
ies examining the subspine distribution of actin isoforms as well as exploring
how β- and γ-actin null neurons may respond differentially to Ca 2+ signals
during LTP will likely shed light on this unexplored topic.
6. INSIGHTS INTO ACTIN ISOFORM FUNCTIONS FROM
IN VIVO STUDIES AND HUMAN DISEASES
Thus far we have reviewed the roles and regulation of actin isoforms
as it pertains to neuronal development and function. It is important to note,
however, that much of this data were acquired in cell culture systems and
often revealed relatively subtle roles for actin isoforms, making it difficult to
infer what significance the observed effects may have for neuronal devel-
opment and function within the nervous system of an intact organism.
Recently, in vivo mouse models have begun to be generated and used to
assess the physiological significance of the many in vitro roles for β- and
γ-actin. Based on the functions we discussed in the previous section, if
β-actin plays similar roles within mammalian neurons in vivo, one might
predict that a mouse lacking β-actin expression would have profound and