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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2017)
Synapse-to-nucleus communication is essential for neural development, plasticity, and repair. In addition to fast electrochemical signaling, neurons employ a slower mechanism of protein transport from synapse-to-nucleus. This mechanism provides potential advantages, including the encoding of spatial information. Many synaptonuclear signaling proteins are transported from the postsynaptic compartment to the nucleus in an activity-dependent manner. The phosphorylation state of two such proteins, CRTC1 and Jacob, is dependent on the stimulus type. While most studies have focused on postsynaptic synaptonuclear communication, a transcriptional co-repressor, CtBP1, was recently discovered to undergo activity-dependent translocation from the presynaptic compartment to the nucleus. Recent evidence indicates that synapse-to-nucleus communication could be cell type-specific, including the identification of a distinct mechanism of excitation-transcription coupling in inhibitory neurons.
    Cover page: Regulated transport of signaling proteins from synapse to nucleus
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2021)

    The formation and plasticity of neuronal circuits relies on dynamic activity-dependent gene expression. While recent work has revealed the identity of important transcriptional regulators and of genes that are transcribed and translated in response to activity, relatively little is known about the cell biological mechanisms by which activity alters the nuclear proteome of neurons to link neuronal stimulation to transcription. Using nucleus-specific proteomic mapping in silenced and stimulated neurons, we uncovered an understudied mechanism of nuclear proteome regulation: activity-dependent proteasome-mediated degradation. We found that the tumor suppressor protein PDCD4 undergoes rapid stimulus-induced degradation in the nucleus of neurons. We demonstrate that degradation of PDCD4 is required for normal activity-dependent transcription, and that PDCD4 target genes include those encoding proteins critical for synapse formation, remodeling, and transmission. Our findings highlight the importance of the nuclear proteasome in regulating the activity-dependent nuclear proteome, and point to a specific role for PDCD4 as a regulator of activity-dependent transcription in neurons.

      Cover page: Neuronal Activity Regulates the Nuclear Proteome to Promote Activity-Dependent Transcription
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2024)
      Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each others expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development.
        Cover page: An activity-regulated transcriptional program directly drives synaptogenesis.
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