Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders

Matthew E. Klein, Hannah Monday, Bryen A. Jordan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Decades of research have demonstrated that rapid alterations in protein abundance are required for synaptic plasticity, a cellular correlate for learning and memory. Control of protein abundance, known as proteostasis, is achieved across a complex neuronal morphology that includes a tortuous axon as well as an extensive dendritic arbor supporting thousands of individual synaptic compartments. To regulate the spatiotemporal synthesis of proteins, neurons must efficiently coordinate the transport and metabolism of mRNAs. Among multiple levels of regulation, transacting RNA binding proteins (RBPs) control proteostasis by binding to mRNAs and mediating their transport and translation in response to synaptic activity. In addition to synthesis, protein degradation must be carefully balanced for optimal proteostasis, as deviations resulting in excess or insufficient abundance of key synaptic factors produce pathologies. As such, mutations in components of the proteasomal or translational machinery, including RBPs, have been linked to the pathogenesis of neurological disorders such as Fragile X Syndrome (FXS), Fragile X Tremor Ataxia Syndrome (FXTAS), and Autism Spectrum Disorders (ASD). In this review, we summarize recent scientific findings, highlight ongoing questions, and link basic molecular mechanisms to the pathogenesis of common neuropsychiatric disorders.

Original languageEnglish (US)
Article number3857934
JournalNeural Plasticity
Volume2016
DOIs
StatePublished - 2016

Fingerprint

Neuronal Plasticity
RNA-Binding Proteins
Fragile X Syndrome
Messenger RNA
Proteins
Nervous System Diseases
Proteolysis
Axons
Learning
Pathology
Neurons
Mutation
Research

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders. / Klein, Matthew E.; Monday, Hannah; Jordan, Bryen A.

In: Neural Plasticity, Vol. 2016, 3857934, 2016.

Research output: Contribution to journalArticle

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