Ubiquitination in Postsynaptic Function and Plasticity

Mabb, Angela M.; Ehlers, Michael

doi:10.1146/annurev-cellbio-100109-104129

Cited by 231 publications

(229 citation statements)

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“…Genetic studies indicate that ubiquitin–proteasome system is necessary for normal human cognitive function by regulating the synapse assembly and elimination (Mabb & Ehlers, 2010). The ubiquitin ligase enzyme Ube3A is a member of the E3 ubiquitin ligase family.…”

Section: Reviewmentioning

confidence: 99%

Autism throughout genetics: Perusal of the implication of ion channels

et al. 2018

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BackgroundAutism spectrum disorder (ASD) comprises a group of neurodevelopmental psychiatric disorders characterized by deficits in social interactions, interpersonal communication, repetitive and stereotyped behaviors and may be associated with intellectual disabilities. The description of ASD as a synaptopathology highlights the importance of the synapse and the implication of ion channels in the etiology of these disorders.MethodsA narrative and critical review of the relevant papers from 1982 to 2017 known by the authors was conducted.ResultsGenome‐wide linkages, association studies, and genetic analyses of patients with ASD have led to the identification of several candidate genes and mutations linked to ASD. Many of the candidate genes encode for proteins involved in neuronal development and regulation of synaptic function including ion channels and actors implicated in synapse formation. The involvement of ion channels in ASD is of great interest as they represent attractive therapeutic targets. In agreement with this view, recent findings have shown that drugs modulating ion channel function are effective for the treatment of certain types of patients with ASD.ConclusionThis review describes the genetic aspects of ASD with a focus on genes encoding ion channels and highlights the therapeutic implications of ion channels in the treatment of ASD.

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Section: Reviewmentioning

confidence: 99%

Autism throughout genetics: Perusal of the implication of ion channels

et al. 2018

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“…Many receptor proteins undergo activity dependent protein degradation by the ubiquitinproteasome system 142 . In postmortem schizophrenia and bipolar disorder tissue, several studies found dysregulation of ubiquitine-proteasome related genes [143][144][145][146][147][148] .…”

Section: Proteasomal Degradation (And Degradation Via Autophagy)mentioning

confidence: 99%

Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?

et al. 2011

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Clathrin mediated endocytosis (CME) is the best characterized mechanism governing cellular membrane-and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the CME interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes, and aberrant neurodevelopment are all influenced by CME, and that other cellular trafficking mechanisms previously linked to psychoses interact with CME in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of CME may offer fruitful opportunities for novel treatments of schizophrenia.

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“…Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels Ubiquitin-mediated protein degradation plays an important role in the regulation of synaptic plasticity, learning, and memory (Ehlers, 2003;Tai and Schuman, 2008;Mabb and Ehlers, 2010). It involves, in addition to an E1 ubiquitin-activating enzyme and an E2 ubiquitin-conjugating enzyme, an E3 ubiquitin-protein ligase that transfers activated ubiquitin to one or more specific substrate proteins.…”

Section: Introductionmentioning

confidence: 99%