![]() ![]() ![]() We first investigated whether Pum2 expression in the brain is developmentally regulated. In this study, we set out to study the role of Pum2 in the activity-independent morphogenesis of dendrites, dendritic spines, and excitatory synapses of rat hippocampal neurons. Recently, Pum2 has also been linked to micro-RNA-regulated activity-dependent dendritogenesis in mammalian neurons ( 10). Its punctate microtubule-associated expression pattern in dendrites mimics that of RNA-binding proteins (RBPs) known to be involved in RNA transport and translational control ( 8, 9). A homolog of Pum, mammalian Pum2, is expressed in hippocampal neurons and is found in ribonucleoparticles (RNPs) in the somatodendritic compartment ( 7). Finally, loss of pumilio impairs long-term memory ( 6). Third, Pum inhibits neuronal excitability by repressing the translation of a voltage-gated sodium channel ( 4, 5). Second, Pum regulates synaptic growth and function by controlling the expression of eIF4E mRNA at the Drosophila neuromuscular junction ( 2, 3). First, Pum controls dendrite morphogenesis in Drosophila peripheral neurons ( 1). In Drosophila, Pumilio (Pum), a member of the Pum and FBF (PuF) family of proteins, plays an important role in the nervous system. ![]() Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. 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. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. 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 Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. ![]()
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