Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function.
In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control.
Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna,1090 Vienna, Austria.
John P
JP
Vessey
Lucia
L
Schoderboeck
Ewald
E
Gingl
Ettore
E
Luzi
Julia
J
Riefler
Francesca
F
Di Leva
Daniela
D
Karra
Sabine
S
Thomas
Michael A
MA
Kiebler
Paolo
P
Macchi
D000818:Animals; D003712:Dendrites / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004594:Electrophysiology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D008156:Luciferases; D009024:Morphogenesis / Q000235:genetics* / Q000502:physiology; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D039561:Eukaryotic Initiation Factor-4E; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C539713:PUM2 protein, rat; D016601:RNA-Binding Proteins; C568250:Scn1a protein, rat; D015222:Sodium Channels; D008156:Luciferases