The Translational Repressor Pumilio Regulates Presynaptic Morphology and Controls Postsynaptic Accumulation of Translation Factor eIF-4E

Abstract

Translational repression by Drosophila Pumilio (Pum) protein controls posterior patterning during embryonic development. Here, we show that Pum is an important mediator of synaptic growth and plasticity at the neuromuscular junction (NMJ). Pum is localized to the postsynaptic side of the NMJ in third instar larvae and is also expressed in larval neurons. Neuronal Pum regulates synaptic growth. In its absence, NMJ boutons are larger and fewer in number, while Pum overexpression increases bouton number and decreases bouton size. Postsynaptic Pum negatively regulates expression of the translation factor eIF-4E at the NMJ, and Pum binds selectively to the 3'UTR of eIF-4E mRNA. The GluRIIa glutamate receptor is upregulated in pum mutants. These results, together with genetic epistasis studies, suggest that postsynaptic Pum modulates synaptic function via direct control of eIF-4E expression.

Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function

“…Our work also suggests an interesting mechanism of translational control within transport particles (2,20). In Drosophila, Pum binds a series of transcripts, with one example being eIF4E (2, 4).…”

“…In Drosophila, Pum binds a series of transcripts, with one example being eIF4E (2, 4). eIF4E has been shown to be part of translational particles near synapses (2). Knock-down of Pum led to an increase in eIF4E, and it was concluded that Pum was negatively regulating the translation of eIF4E.…”

“…First, Pum controls dendrite morphogenesis in Drosophila peripheral neurons (1). Second, Pum regulates synaptic growth and function by controlling the expression of eIF4E mRNA at the Drosophila neuromuscular junction (2,3). Third, Pum inhibits neuronal excitability by repressing the translation of a voltage-gated sodium channel (4,5).…”

Pumilio Puf domain RNA-binding proteins in Arabidopsis

“…For example, Drosophila Pum and mammalian Pumilio 2 proteins control the abundance of eIF-4E mRNA by binding its 3'UTR and mediating its decay. 26,27 However, recently mammalian Pumilio 2 was shown to interfere with translation control through a non-decay pathway by competing with eIF-4E protein for access to the 7-methyl guanosine cap and repressing the initiation of translation by outcompeting eIF-4E, thereby preventing formation of the initiation complex. 28 Hence, certain Pumilio proteins appear to play a role in the initiation of translation by controlling eIF-4E.…”

“…It is also possible that APUM23 interacts with translation initiation factors, such as eIF-4E, and mediates translation control, as do mammalian Puf proteins, 28 or it may bind to the 3'UTR of eIF-4E mRNA to control its translation. 26,27 The increased sensitivity of apum23-1 to cycloheximide, a eukaryotic protein synthesis inhibitor and its resistance to the antibiotic streptomycin, argue in favor of the involvement of APUM23 in the control of translation and ribosome biogenesis. Ribosomal proteins and rRNA together constitute the structural components of the ribosomes.…”