Molecular mechanisms shaping the actin filament scaffold of dendritic filopodia

Dendritic spines are the postsynaptic compartment of most excitatory synapses in the vertebrate brain. Their morphology is defined by a complex actin scaffold consisting of branched and unbranched actin filaments (F-actin), which constitute the major structural component of dendritic spines. During brain development, dendritic spines arise from dendritic filopodia, motile finger-like dendritic protrusions, whose morphology is also defined by an actin scaffold. The organization of the actin scaffold as well as its dynamic behavior in both dendritic filopodia and dendritic spines requires the coordinated activity of actin binding proteins (ABP) that promote either assembly or disassembly of F-actin. Studies of the past two decades identified a number of ABP and upstream regulatory pathways that control the morphology of dendritic spines as well as their morphological changes associated with synaptic plasticity, the cellular basis for learning and memory. Instead, much less is known about actin regulatory mechanisms that control the formation and elongation of dendritic filopodia or the structural changes associated with their transition into dendritic spines. This review article highlights recent advances in the field by summarizing and discussing studies of the past few years that provided exciting novel insights into the molecular machinery that governs dendritic filopodia initiation and their maturation into dendritic spines.