![]() ![]() ![]() However, these changes were not permanent, and “stabilization” of mature morphology required a longer time. Rapid changes from filopodia-like to mushroom-shaped morphology were detected in DIV 14 neurons (Fig. These data suggest that ADF/cofilins may be central to dendritic spine morphogenesis and dynamics.Īs described previously ( Takahashi et al., 2003 Oray et al., 2006), hippocampal neurons presented typical morphological changes, starting from filopodia-like protrusions (8 d in vitro ), progressing to spines with a reasonably long neck and small head (DIV 14), and finally changing to spines with a short neck and a large bulbous head (DIV 21 Fig. Furthermore, ADF/cofilin phosphorylation is related to the formation of long-term potentiation and increased spine head volume ( Fukazawa et al., 2003 Chen et al., 2007 Fedulov et al., 2007) correspondingly, ADF/cofilin dephosphorylation has been linked to long-term depression and spine shrinkage ( Zhou et al., 2004). However, in addition to ADF/cofilins, LIM kinases do have other substrates, such as transcription factors CREB and Nurr1 ( Yang et al., 2004 Sacchetti et al., 2006). LIM kinases, which inhibit actin filament disassembly by phosphorylating ADF/cofilins, are necessary for normal spine development ( Meng et al., 2002, 2004). ![]() Two ADF/cofilin isoforms occur in the vertebrate central nervous system ( Vartiainen et al., 2002), and they localize within the postsynaptic density in dendritic spines ( Racz and Weinberg, 2006). Finally, we show that perturbation of these key steps in actin dynamics results in altered synaptic transmission.Īctin-depolymerizing factor (ADF)/cofilins, which sever and depolymerize aged actin filaments, are also central regulators of cytoskeletal dynamics in many cell types ( Bamburg, 1999). Actin filament nucleation through the Arp2/3 complex subsequently promotes spine head expansion, and ADF/cofilin-induced actin filament disassembly is required to maintain proper spine length and morphology. The small GTPase Rif and its effector mDia2 formin play a central role in regulating actin dynamics during filopodia elongation. We show that the filopodia-like precursors of dendritic spines elongate through actin polymerization at both the filopodia tip and root. Despite the pivotal role of the actin cytoskeleton in spine morphogenesis, little is known about the mechanisms regulating actin filament polymerization and depolymerization in dendritic spines. Morphological changes in these actin-rich structures are associated with learning and memory formation. Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in the mature brain. ![]()
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