Biology Reference
In-Depth Information
Abstract
The actin cytoskeleton contributes directly or indirectly to nearly every aspect of
neuronaldevelopmentand function.Thisdiversityof functions isoftenattributed to
actin regulatory proteins, although how the composition of the actin cytoskeleton
itselfmayinfluenceitsfunctionisoftenoverlooked.Inneurons,theactincytoskeleton
iscomposedoftwodistinct isoforms, β -and γ -actin.Functionsfor β -actinhavebeen
investigated in axon guidance, synaptogenesis, and disease. Insight from loss-of-
function in vivostudieshasalso revealednovel roles for β -actin inselectbrainstruc-
turesandbehaviors.Conversely,very little isknown regarding functionsof γ -actin in
neurons.Thedysregulationormutationofboth β -and γ -actinhasbeenimplicatedin
multiple human neurological disorders, however, demonstrating the critical impor-
tanceofthesestillpoorlyunderstoodproteins.Thischapterhighlightswhatiscurrently
knownregardingpotentialdistinctfunctionsfor β -and γ -actininneuronsaswellasthe
significantareasthatremainunexplored.
1. INTRODUCTION
While significant previous work has focused on the role of actin-bind-
ing proteins in regulating actin dynamics in neurons, one often overlooked
aspect of actin biology is how the composition of the actin cytoskeleton
itself influences its function. The goal of this chapter is to present what is
currently known about the contribution of individual actin isoforms to the
maintenance and function of the actin cytoskeleton in neuronal develop-
ment and function. We will also highlight the significant areas that remain
unexplored.
2. NEURONAL ACTIN CYTOSKELETON
The actin cytoskeleton contributes directly or indirectly to nearly
every facet of neuronal development and function, and thus the impact of
this ubiquitous protein cannot be overstated. Beginning with the birth of a
neuron, an actin-based contractile ring facilitates the cellular cleavage event
separating the postmitotic neuron from its neural progenitor cell ( Levayer
and Lecuit, 2012 ). Soon after, actin dynamics contribute to propelling
newly generated neurons from their birthplace to destinations throughout
the brain ( Ayala et al., 2007 ). Later, axons capped by growth cones elongate
in search of proper synaptic targets amidst a complex and constantly chang-
ing environment ( Lowery andVanVactor, 2009 ). The actin cytoskeleton not
only provides a structural scaffold for the growth cone but also contributes
to its guided migration facilitating the proper pathfinding of axons and
assembly of neural wiring ( Dent and Gertler, 2003 ). As neurons mature and
 
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