Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, DE-NOVO MUTATIONS, REGULATORY SUBUNIT, SUBCELLULAR-LOCALIZATION, INTELLECTUAL DISABILITY, TYROSINE-HYDROXYLASE, CRYSTAL-STRUCTURE, PHOSPHORYLATION, PPP2R5D, BINDING, DEPHOSPHORYLATION, PP2A, PP2A syndromes, neurodevelopmental disorders, protein phosphatases, Animals, Brain, Humans, Intellectual Disability, Isoenzymes, Mice, Mutation, Neurodevelopmental Disorders, Protein Phosphatase 2, Substrate Specificity, 12X4222N#56289382, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, 3101 Biochemistry and cell biology

Abstract:

By removing Ser/Thr-specific phosphorylations in a multitude of protein substrates in diverse tissues, Protein Phosphatase type 2A (PP2A) enzymes play essential regulatory roles in cellular signalling and physiology, including in brain function and development. Here, we review current knowledge on PP2A gene mutations causally involved in neurodevelopmental disorders and intellectual disability, focusing on PPP2CA, PPP2R1A and PPP2R5D. We provide insights into the impact of these mutations on PP2A structure, substrate specificity and potential function in neurobiology and brain development.