Journal article
Protein phosphatase 2A – structure, function and role in neurodevelopmental disorders
Journal of cell science, Vol.134(13)
07/01/2021
DOI: 10.1242/jcs.248187
PMCID: PMC8277144
PMID: 34228795
Abstract
ABSTRACT Neurodevelopmental disorders (NDDs), including intellectual disability (ID), autism and schizophrenia, have high socioeconomic impact, yet poorly understood etiologies. A recent surge of large-scale genome or exome sequencing studies has identified a multitude of mostly de novo mutations in subunits of the protein phosphatase 2A (PP2A) holoenzyme that are strongly associated with NDDs. PP2A is responsible for at least 50% of total Ser/Thr dephosphorylation in most cell types and is predominantly found as trimeric holoenzymes composed of catalytic (C), scaffolding (A) and variable regulatory (B) subunits. PP2A can exist in nearly 100 different subunit combinations in mammalian cells, dictating distinct localizations, substrates and regulatory mechanisms. PP2A is well established as a regulator of cell division, growth, and differentiation, and the roles of PP2A in cancer and various neurodegenerative disorders, such as Alzheimer's disease, have been reviewed in detail. This Review summarizes and discusses recent reports on NDDs associated with mutations of PP2A subunits and PP2A-associated proteins. We also discuss the potential impact of these mutations on the structure and function of the PP2A holoenzymes and the etiology of NDDs.
Details
- Title: Subtitle
- Protein phosphatase 2A – structure, function and role in neurodevelopmental disorders
- Creators
- Priyanka Sandal - University of IowaChian Ju Jong - University of IowaRonald A Merrill - University of IowaJianing Song - University of IowaStefan Strack - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.134(13)
- DOI
- 10.1242/jcs.248187
- PMID
- 34228795
- PMCID
- PMC8277144
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: DK116624; name: Jordan's Guardian Angels; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust, award: Iowa Neuroscience Institute
- Language
- English
- Date published
- 07/01/2021
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984201429302771
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