Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 95

Abstract
Filopodiaarefinger-likecellularprotrusionsfoundthroughoutthemetazoankingdom
andperform fundamentalcellular functionsduringdevelopmentandcellmigration.
Neurons exhibit a wide variety of extremely complexmorphologies. In the nervous
system, filopodia underlie many major morphogenetic events. Filopodia have roles
spanning the initiation and guidance of neuronal processes, axons and dendrites to
theformationofsynapticconnections.Thischapteraddressesthemechanismsofthe
formationanddynamicsofneuronalfilopodia.Someofthemajorlessonslearnedfrom
thestudyofneuronalfilopodiaare(1)therearemultiplemechanismsthatcanregulate
filopodiainacontext-dependentmanner,(2)thatfilopodiaarespecializedsubcellular
domains, (3) that filopodiaexhibitdynamicmembrane recyclingwhich also controls
aspectsof filopodialdynamics, (4) thatneuronal filopodia containmachinery for the
orchestrationoftheactinandmicrotubulecytoskeleton,and(5)localizedproteinsyn-
thesiscontributestoneuronalfilopodialdynamics.
1. INTRODUCTION
Actin is one of the most highly conserved and ancient proteins in
nature. In eukaryotes, along with many associated proteins that regulate
its function, the actin cytoskeleton accounts for up to 10-20% of cellular
protein. Actin is monomeric in solution but through de novo nucleation
and polymerization forms actin filaments. Actin filaments have fundamental
roles in cellular morphogenesis.The evolutionary origins of actin are ancient
and date back to the evolution of bacteria exhibiting cellular morphologies
that deviate from a spherical phenotype ( Cabeen and Jacobs-Wagner, 2010 ),
underscoring the importance of actin in the regulation of cellular morphol-
ogy. Actin filaments form a submembranous cytoskeleton that determines
cell shape and is required for the outward protrusion and maintenance of
the cell edges. The major protrusive structures formed by actin filaments are
lamellipodia and filopodia (Fig. 3 . 1 A). These protrusive structures allow the
cell to probe and sense its environment, and also accordingly alter its shape
and motility. This chapter reviews the cellular mechanisms that give rise to
filopodia, focusing on lessons learned from the study of neurons.
Neuronal filopodia are dynamic finger-like projections extending out-
ward from the surface of cells (Fig. 3 . 1 B). They are usually initiated as small
nubs protruding from the cell surface. The nub subsequently elongates giv-
ing rise to a shaft. Neuronal filopodia generally attain maximal lengths in
the range of 5-10 µm, but can occasionally extend up to tens of microm-
eters from the site of initiation. The width of filopodia is on the range of
100-900 nm. Filopodia are dynamic and can exhibit a variety of behaviors
including lateral bending of the entire filopodium and bending at hinge