Pumilio2 and Staufen2 selectively balance the synaptic proteome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA726236 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14362391_1.fastq.gz | Fastqsanger.gz | |||
| SRR14362391_2.fastq.gz | Fastqsanger.gz | |||
| SRR14362392_1.fastq.gz | Fastqsanger.gz | |||
| SRR14362392_2.fastq.gz | Fastqsanger.gz | |||
| SRR14362393_1.fastq.gz | Fastqsanger.gz |
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Project description:Cells, in particular neurons, have the capacity to adapt to environmental stimuli, a phenomenon termed cellular plasticity. The underlying processes are controlled by a network of RNA-binding proteins (RBPs). Their impact on cellular plasticity, however, is largely unknown. To address this important question, we chose Pumilio2 (Pum2) and Staufen2 (Stau2) that both regulate synaptic transmission. Surprisingly, even though both RBPs dynamically interact with each other in neurons, their respective impact on the transcriptome and proteome is highly selective. While Pum2 deficiency leads to reduced translation and protein expression, Stau2 depletion preferentially impacts RNA levels and increases protein abundance. Furthermore, we show that Pum2 activates expression of key GABAergic synaptic components, e.g. the GABAA receptor scaffold protein Gephyrin. Consequently, Pum2 depletion selectively reduced the amplitude of miniature inhibitory postsynaptic currents. Together, our data clearly demonstrate that RBPs are needed to maintain proteostasis in order to control distinct signaling pathways which critically balance synaptic transmission.
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Project description:Cells, in particular neurons, have the capacity to adapt to environmental stimuli, a phenomenon termed cellular plasticity. The underlying processes are controlled by a network of RNA-binding proteins (RBPs). Their impact on cellular plasticity, however, is largely unknown. To address this important question, we chose Pumilio2 (Pum2) and Staufen2 (Stau2) that both regulate synaptic transmission. Importantly, even though both RBPs dynamically interact with each other in neurons, their respective impact on the transcriptome and proteome is highly selective. While Pum2 deficiency leads to reduced translation and protein expression, Stau2 depletion preferentially impacts RNA levels and increases protein abundance. Furthermore, Pum2 activates expression of key GABAergic synaptic components, e.g. the GABAA receptor scaffold protein Gephyrin. Consequently, Pum2 depletion selectively reduced the amplitude of miniature inhibitory postsynaptic currents. Together, our data demonstrate that RBPs are needed to maintain proteostasis in order to control distinct signaling pathways which critically balance synaptic transmission.
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Project description:Li2012 Calcium mediated synaptic
plasticity
This model is an extension of
BIOMD0000000183.
This model is described in the article:
Calcium input frequency,
duration and amplitude differentially modulate the relative
activation of calcineurin and CaMKII.
Li L, Stefan MI, Le Novère
N.
PLoS ONE 2012; 7(9): e43810
Abstract:
NMDA receptor dependent long-term potentiation (LTP) and
long-term depression (LTD) are two prominent forms of synaptic
plasticity, both of which are triggered by post-synaptic
calcium elevation. To understand how calcium selectively
stimulates two opposing processes, we developed a detailed
computational model and performed simulations with different
calcium input frequencies, amplitudes, and durations. We show
that with a total amount of calcium ions kept constant, high
frequencies of calcium pulses stimulate calmodulin more
efficiently. Calcium input activates both calcineurin and
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) at all
frequencies, but increased frequencies shift the relative
activation from calcineurin to CaMKII. Irrespective of
amplitude and duration of the inputs, the total amount of
calcium ions injected adjusts the sensitivity of the system to
calcium input frequencies. At a given frequency, the quantity
of CaMKII activated is proportional to the total amount of
calcium. Thus, an input of a small amount of calcium at high
frequencies can induce the same activation of CaMKII as a
larger amount, at lower frequencies. Finally, the extent of
activation of CaMKII signals with high calcium frequency is
further controlled by other factors, including the availability
of calmodulin, and by the potency of phosphatase
inhibitors.
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2024-09-02 | BIOMD0000000628 | BioModels