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期刊名称: neurogenetics
Volume:16    Issue:3        Page:215-221
ISSN:1364-6745

A defect in the retromer accessory protein, SNX27, manifests by infantile myoclonic epilepsy and neurodegeneration期刊论文

作者: Damseh Nadirah Danson Chris M Al-Ashhab Motee Abu-Libdeh Bassam Gallon Matthew
DOI:10.1007/s10048-015-0446-0

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页码: 215-221
被引频次: 25
出版者: Springer Berlin Heidelberg,SPRINGER,Springer Science & Business Media,Springer,Springer Nature B.V
期刊名称: neurogenetics
ISSN: 1364-6745
卷期: Volume:16    Issue:3
语言: English
摘要: The composition of the neuronal cell surface dictates synaptic plasticity and thereby cognitive development. This remodeling of the synapses is governed by the endocytic network which internalize transmembrane proteins, then sort them back to the cell surface or carry them to the lysosome for degradation. The multi-protein retromer complex is central to this selection, capturing specific transmembrane proteins and remodeling the cell membrane to form isolated cargo-enriched transport carriers. We investigated a consanguineous family with four patients who presented in infancy with intractable myoclonic epilepsy and lack of psychomotor development. Using exome analysis, we identified a homozygous deleterious mutation in SNX27, which encodes sorting nexin 27, a retromer cargo adaptor. In western analysis of patient fibroblasts, the encoded mutant protein was expressed at an undetectable level when compared with a control sample. The patients’ presentation and clinical course recapitulate that reported for the SNX27 knock-out mouse. Since the cargo proteins for SNX27-mediated sorting include subunits of ionotropic glutamate receptors and endosome-to-cell surface synaptic insertion of AMPA receptors is severely perturbed in SNX27−/− neurons, it is proposed that at least part of the neurological aberrations observed in the patients is attributed to defective sorting of ionotropic glutamate receptors. SNX27 deficiency is now added to the growing list of neurodegenerative disorders associated with retromer dysfunction.
相关主题: Human Genetics, Myoclonic epilepsy, Neurosciences, Biomedicine, SNX27, Retromer complex, Molecular Medicine, DEPENDENT TRAFFICKING, POTASSIUM CHANNELS, ALZHEIMERS-DISEASE, GOLGI RETROGRADE TRANSPORT, PARKINSON DISEASE, MAMMALIAN RETROMER, MEDIATED ENDOSOME, PLASMA-MEMBRANE, CLINICAL NEUROLOGY, SORTING NEXIN 27, WASH COMPLEX, GENETICS & HEREDITY, Proteins, Neurodegeneration, Epilepsy, alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, Neurodegenerative diseases, Glutamic acid receptors (ionotropic), Cognitive ability, Lysosomes, Cell membranes, adaptor proteins, Cell surface, Membrane proteins, Plasticity (synaptic), Fibroblasts, nexin, Mutation, Protein transport, Synapses, Sorting Nexins - genetics, Sorting Nexins - deficiency, Brain - physiopathology, Humans, Infant, Male, Neurodegenerative Diseases - genetics, Pedigree, Brain - pathology, Female, Infant, Newborn, Epilepsies, Myoclonic - genetics, Fibroblasts - metabolism, Glutamate, Analysis,

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