气候变化领域集成服务门户(CCPortal): Early role for a Na+,K+-ATPase (ATP1A3) in brain development

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DOI	10.1073/pnas.2023333118
	Early role for a Na+,K+-ATPase (ATP1A3) in brain development
	Smith R.S.; Florio M.; Akula S.K.; Neil J.E.; Wang Y.; Sean Hill R.; Goldman M.; Mullally C.D.; Reed N.; Bello-Espinosa L.; Flores-Sarnat L.; Monteiro F.P.; Erasmo C.B.; Vairo F.P.E.; Morava E.; James Barkovich A.; Gonzalez-Heydrich J.; Brownstein C.A.; McCarroll S.A.; Walsh C.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:25
英文摘要	Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function catalyzed by the Na+,K+-ATPase α-subunit. Here, we describe ATP1A3 variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we built an ATP1A3 transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex. We found that fetal expression of ATP1A3 is most abundant to a subset of excitatory neurons carrying transcriptional signatures of the developing subplate, yet also maintains expression in nonneuronal cell populations. Moving forward a year in human development, we profiled ∼52,000 nuclei from four areas of an infant neocortex and show that ATP1A3 expression persists throughout early postnatal development, most predominantly in inhibitory neurons, including parvalbumin interneurons in the frontal cortex. Finally, we discovered the heteromeric Na+,K+-ATPase pump complex may form nonredundant cell-type–specific α-β isoform combinations, including α3-β1 in excitatory neurons and α3-β2 in inhibitory neurons. Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for α3 in human cortex development, as well as a cell-type basis for pre- and postnatal ATP1A3-associated diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ATP1A3; Cortex development; cortical malformation; developmental channelopathy; polymicrogyria
语种	英语
scopus关键词	adenosine triphosphatase (potassium sodium); adenosine triphosphatase (potassium); integrin; levetiracetam; messenger RNA; oxcarbazepine; parvalbumin; phenobarbital; protein alpha3beta2 integrin; unclassified drug; very late activation antigen 3; adenosine triphosphatase (potassium sodium); ATP1A3 protein, human; messenger RNA; parvalbumin; Article; ATP1A3 gene; brain cortex; brain development; brain ischemia; brain radiography; brain tissue; case report; cell population; child; clinical article; clubfoot; controlled study; cytology; developmental delay; electroencephalography; feeding difficulty; female; frontal cortex; gene expression; genetic code; genetic profile; genetic transcription; genetic variability; hemiparesis; hip dysplasia; hospital admission; hospital discharge; human; human cell; human tissue; hydronephrosis; hypersalivation; hyporeflexia; in situ hybridization; infant; jaundice; Lennox Gastaut syndrome; male; microcephaly; microgyria; muscle hypertonia; muscle hypotonia; neocortex; neurologic examination; newborn intensive care; nuclear magnetic resonance imaging; nystagmus; phenotype; physical examination; postnatal development; prediction; protein function; respiratory distress; school child; seizure; single cell RNA seq; transcriptomics; whole exome sequencing; adult; brain; diagnostic imaging; embryology; enzymology; fetus; gene expression regulation; genetics; interneuron; metabolism; microgyria; mutation; nerve cell; newborn; single cell analysis; Adult; Brain; Child; Female; Fetus; Gene Expression Regulation, Developmental; Humans; Infant; Infant, Newborn; Interneurons; Magnetic Resonance Imaging; Male; Mutation; Neocortex; Neurons; Parvalbumins; Phenotype; Polymicrogyria; RNA, Messenger; Single-Cell Analysis; Sodium-Potassium-Exchanging ATPase
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251148
作者单位	Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Howard Hughes Medical Insitute, Boston Children’s Hospital, Boston, MA 02115, United States; Department of Pediatrics and Neurology, Broad Institute of MIT and Harvard, Harvard Medical School, Boston, MA 02115, United States; Department of Genetics, Harvard Medical School, Boston, MA 02115, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Harvard-MIT MD/PhD Program, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, United States; Arnold Palmer Hospital for Children, Orlando, FL 32806, United States; Department of Paediatrics and Clinical Neurosciences, Owerko Centre, University of Calgary, Alberta Children’s Hospital Research Institute, Calgary, AB T2N 1N4, Canada; Mendelics Genomic Analysis, São Paulo, CEP 04013-000, Brazil; Children’s Institute, Hospital das Clinicas, São Paulo, CEP 05403-000, Brazil; Center for Individualize...
推荐引用方式 GB/T 7714	Smith R.S.,Florio M.,Akula S.K.,et al. Early role for a Na+,K+-ATPase (ATP1A3) in brain development[J],2021,118(25).
APA	Smith R.S..,Florio M..,Akula S.K..,Neil J.E..,Wang Y..,...&Walsh C.A..(2021).Early role for a Na+,K+-ATPase (ATP1A3) in brain development.Proceedings of the National Academy of Sciences of the United States of America,118(25).
MLA	Smith R.S.,et al."Early role for a Na+,K+-ATPase (ATP1A3) in brain development".Proceedings of the National Academy of Sciences of the United States of America 118.25(2021).