ATP8A2
- Known as:
- ATP8A2
- Catalog number:
- 002258A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATP8A2
Related genes to: ATP8A2
- Gene:
- ATP8A2 NIH gene
- Name:
- ATPase phospholipid transporting 8A2
- Previous symbol:
- -
- Synonyms:
- ATPIB, ML-1
- Chromosome:
- 13q12.13
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-25
- Date modifiied:
- 2016-10-05
Related products to: ATP8A2
Related articles to: ATP8A2
- Phospholipid asymmetry in cellular membranes is maintained by flippases. ATP8A1 and ATP8A2 are the principal flippases of phosphatidylserine (PS) in the mammalian nervous system; however, their specific physiological roles and potential functional redundancy remain incompletely characterized. Here, we show that ATP8A1/ATP8A2 double-knockout mice displayed more severe growth retardation than ATP8A2 knockout mice, indicating that ATP8A1 and ATP8A2 play redundant roles. In hippocampal neurons, ATP8A2 was highly enriched at inhibitory post-synapses. Surface biotinylation assays revealed increased surface GABA receptor levels of hippocampal neurons deficient for ATP8A1 or ATP8A2. Mechanistically, our data support a model in which ATP8A2, but not ATP8A1, regulates local membrane lipid asymmetry, thereby facilitating dynamin2 recruitment and promoting GABA receptor endocytosis. Collectively, ATP8A1 and ATP8A2 share overlapping roles in postnatal growth, while they contribute to neural function by modulating inhibitory synaptic transmission through distinct mechanisms. - Source: PubMed
Publication date: 2026/06/30
Kawase MuneyukiTokunaga ShuUmemura YutaShawki Hossam HOmi JumpeiHoshiai AyanaOhshima TomohaNakajima TsuzumiKohno TakaoSakurai TakashiAoki JunkenOishi HisashiHattori Mitsuharu - Phosphatidylserine (PS) asymmetry in plasma membranes is critical for cellular functions and serves as an apoptotic signal in many cell types. However, in mature neurons, the molecular mechanisms governing PS distribution, its precise regulation, and its functional significance beyond apoptosis and development remain poorly understood - particularly in the context of neurodegeneration. Here, we mapped the spatiotemporal dynamics of PS exposure in mature hippocampal neurons under physiological and pathological conditions using time-lapse imaging, revealing specific PS externalization hotspots at dendritic branching points. Using multiple in vitro and in vivo neurodegeneration models combined with molecular modeling, RNA interference, pharmacological interventions, and biochemical assays, we identified Atp8a2 as the primary regulator of PS asymmetry in mature neurons beyond its known roles in development. Notably, Atp8a2 expression levels - rather than its flippase activity alone - were essential for maintaining neuronal structural integrity and viability. Atp8a2 expression was significantly altered by neurotoxic stimuli and in multiple mouse models of neurodegeneration. Reduced Atp8a2 expression led to increased PS exposure, compromised neuronal architecture, and heightened susceptibility to degeneration, whereas Atp8a2 overexpression conferred substantial neuroprotection. The distinction between Atp8a2's enzymatic activity and expression level reveals a mechanism of neuronal homeostasis linking PS regulation to structural integrity and survival, possibly through association with cytoskeletal protein networks. Thus, Atp8a2 expression is a critical determinant of mature neuronal viability, presenting a potential target for neuroprotective strategies in neurodegeneration. - Source: PubMed
Publication date: 2026/07/22
Schneider AdrianaMerkel Alexandra BPerta NunzioRuff LisaUssyshkin NettaZimmer PaulaAksan BaharLepeuve AmandineD'Andrea LauraPelucchi SilviaMarcello ElenaDi Marino DanieleMauceri Daniela - Intellectual disability (ID) affects approximately 1%-3% of the population and spans diverse clinical presentations with marked genetic heterogeneity, especially in consanguineous populations where autosomal-recessive ID is common. Despite advances in diagnostic methods, ~50% of individuals with ID remain without a molecular diagnosis. Genome sequencing (GS) can detect variant classes poorly captured by other methodologies, including deep intronic splice changes and structural variants. We performed short-read GS on 38 Iranian autosomal recessive intellectual disability (ARID) families that remained unsolved after exome sequencing (ES) and two phases of reanalysis. Sequencing and variant calling were performed on DRAGEN Bio-IT Platform with GRCh38 and variants were annotated in Golden helix Varseq software and the AnnotSV tool. GS yielded diagnoses in 2 of 38 families (5.3%), identifying a homozygous deep-intronic variant (c.1473 + 519C > T) that creates a cryptic donor site and a 57-bp pseudoexon, and a homozygous ~103-kb deletion removing the in-frame Exon 2. Additionally, GS uncovered a homozygous missense variant that represents a novel candidate gene for ARID, but further studies are required to confirm the gene-disease association. The and variants were uniquely detectable by GS. In conclusion, in a challenging, ES-negative ARID cohort, GS provided an additional ~5.3% diagnostic yield by uncovering a noncoding splice alteration and a large intragenic deletion. These results underscore GS as a valuable, though still modest, tool over ES and highlight significant interpretation challenges in noncoding regions. Continued advances in functional assays and complementary long-read technologies will be essential to further reduce the diagnostic gap in unresolved ID. - Source: PubMed
Publication date: 2026/07/01
Shokouhian EbrahimMoslemi MasoumehMoghadam Masoumeh GoleyjaniMolaei NegarAlagha ParnianReshadmanesh AzadehArzhangi SanazGhodratpour FatemehCelik MertKadioglu Ilayda SelcenEdizadeh MasoudAkbari Mohammad RezaKahrizi KimiaNajmabadi Hossein - Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ)-related disorders are rare, nonprogressive, autosomal recessive conditions primarily characterized by cerebellar ataxia, hypotonia, intellectual disability, delayed ambulation, and, in some cases, quadrupedal locomotion. Pathogenic variants in four disease genes, , , , and have been linked to these disorders, with cases reported across various ethnic groups and geographic regions. However, no reports of CAMRQ1 (OMIM #224050) have been previously made from Africa. In this study, we report the first African family with four affected siblings exhibiting typical CAMRQ1 clinical features with varying levels of phenotypic severity. Genetic analysis revealed a novel missense homozygous variant (c.1694C > A; p.P565Q) in the gene in all the affected individuals, with the parents being heterozygous. Biochemical analysis, including immunofluorescence and confocal laser microscopy, western blot, and endoglycosidase H sensitivity and resistance assay, demonstrated the retention of the p.(P565Q) VLDLR protein in the endoplasmic reticulum (ER), impairing its trafficking to the plasma membrane and thus confirming its pathogenic impact. This ER retention is expected to disrupt VLDLR-mediated signaling pathways, including reelin signaling, thereby affecting neuronal migration. Furthermore, due to its ER retention, the p.(P565Q) is expected to induce ER stress and activate the endoplasmic reticulum-associated degradation (ERAD) pathway. Our findings expand the genetic and geographical spectrum of CAMRQ1 and provide further functional insights into its underlying pathogenesis. - Source: PubMed
Publication date: 2026/04/27
Jawabri Aseel ASalazar-Villacorta AinaraSenghor HenrietteNdiaye RokhayaAl-Mehrzi AliaDiop Amadou GalloNdiaye MoustaphaAli Bassam RRodriguez Cruz Pedro M - : Parental imprinting plays a crucial role in epigenetic regulation and is increasingly recognized for its involvement in neurodevelopmental disorders. Although is considered a non-imprinted gene; However, the marked phenotypic variability observed across related disorders suggests that additional regulatory layers may influence its expression. : We investigated the imprinting-like status of through functional analyses of a splicing variant (c.1580-3C>G) identified in a patient diagnosed with Cerebellar Ataxia, Mental Retardation, and Disequilibrium syndrome type 4 (CAMRQ4). Sanger sequencing was used to assess allelic expression and identify aberrant transcripts. : Our analyses revealed an allelic expression imbalance suggestive of parental imprinting of . Moreover, Sanger sequencing led to the identification of a novel - chimeric transcript, pointing to a previously unreported transcriptional event, the functional relevance of which remains to be determined. : These findings indicate that may be subject to imprinting-like regulation and involved in atypical splicing events with unknown significance. This highlights the need for further investigation into the epigenetic and transcriptional complexity of -related neurodevelopmental disorders. - Source: PubMed
Publication date: 2026/04/06
Bouramtane AbdelhamidElmakhzen BadreddineOuskri AmalAhakoud MohamedBouguenouch LailaOuldim KarimAskander Omar