A dynamin-3 spliced variant modulates the actin/cortactin-dependent morphogenesis of dendritic spines.
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.
Gray
Noah W
NW
Molecular Neuroscience Program and Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
Kruchten
Anne E
AE
Chen
Jing
J
McNiven
Mark A
MA
D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D051356:Cortactin; D003712:Dendrites / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D034286:Dynamin III / Q000737:chemistry* / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D047468:Immunoprecipitation; D046911:Macromolecular Substances; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D011554:Pseudopodia / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D000199:Actins; D051356:Cortactin; C495870:Cttn protein, rat; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins; D012313:RNA; D020558:GTP Phosphohydrolases; D034286:Dynamin III