Immature dendrites extend many actin-rich filopodial structures that can be replaced by synapse-containing dendritic spines as the neuron matures. The large GTPase dynamin-3 (Dyn3) is a component of the postsynapse in hippocampal neurons but its function is undefined. Here, we demonstrate that a specific Dyn3 variant (Dyn3baa) promotes the formation of immature dendritic filopodia in cultured neurons. This effect is dependent upon Dyn3 GTPase activity and a direct interaction with the F-actin-binding protein cortactin. Consistent with these findings, Dyn3baa binds to cortactin with a 200% higher affinity than Dyn3aaa, a near identical isoform that does not induce dendritic filopodia when expressed in cultured neurons. Finally, levels of Dyn3baa-encoding mRNA are tightly regulated during neuronal maturation and are markedly upregulated during synaptogenesis. Together, these findings provide the first evidence that an enhanced interaction between a specific Dyn3 splice variant and cortactin modulate actin-membrane dynamics in developing neurons to regulate the morphogenesis of dendritic spines.
Supplementary material available online at http://jcs.biologists.org/cgi/content/full/118/6/1279/DC1
Noah W. Gray, Anne E. Krutchten, Jing Chen, & Mark A. McNiven
A dynamin-3 spliced variant modulates the actin/cortactin-dependent morphogenesis of dendritic spines.
Journal of Cell Science, 2005, volume 118, issue 6, pages 1279-1290
Gray, Noah W.; Kruchten, Anne E.; Chen, Jing; and McNiven, Mark A., "A Dynamin-3 Spliced Variant Modulates the Actin/Cortactin-Dependent Morphogenesis of Dendritic Spines" (2005). Faculty Publications. Published Version. Submission 4.