Unknown

Dataset Information

0

?-synuclein assemblies sequester neuronal ?3-Na+/K+-ATPase and impair Na+ gradient.

ABSTRACT: Extracellular ?-synuclein (?-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that ?-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the ?3-subunit of Na+/K+-ATPase (NKA) as a cell surface partner of ?-syn assemblies. The interaction strength depended on the state of ?-syn, fibrils being the strongest, oligomers weak, and monomers none. Mutations within the neuron-specific ?3-subunit are linked to rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). We show that freely diffusing ?3-NKA are trapped within ?-syn clusters resulting in ?3-NKA redistribution and formation of larger nanoclusters. This creates regions within the plasma membrane with reduced local densities of ?3-NKA, thereby decreasing the efficiency of Na+ extrusion following stimulus. Thus, interactions of ?3-NKA with extracellular ?-syn assemblies reduce its pumping activity as its mutations in RDP/AHC.

SUBMITTER: Shrivastava AN 

PROVIDER: S-EPMC4601662 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that α-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the α3-subunit of Na+/K+-ATPase (NKA) as a cell surface partner of α-syn assemblies. The interaction strength depended on the state of α-syn, fibrils being the strongest, oligomers weak,  ...[more]

Similar Datasets

Unknown ?-Synuclein oligomers impair neuronal microtubule-kinesin interplay.
| S-EPMC3724632 | biostudies-literature
Unknown Extracellular Na(+) levels regulate formation and activity of the NaX/alpha1-Na(+)/K(+)-ATPase complex in neuronal cells.
| S-EPMC4255601 | biostudies-literature
Transcriptomics Na,K-ATPase alpha 1 het. heart
2004-11-19 | GSE1134 | GEO
Unknown C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins.
| S-EPMC5138863 | biostudies-literature
Unknown Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase.
| S-EPMC2234217 | biostudies-literature
Unknown Nanoparticles With Affinity for α-Synuclein Sequester α-Synuclein to Form Toxic Aggregates in Neurons With Endolysosomal Impairment.
| S-EPMC8565355 | biostudies-literature
Genomics Pyrgomorphid grasshopper Na,K-ATPase
| PRJEB31295 | ENA
Unknown Nucleopeptide Assemblies Selectively Sequester ATP in Cancer Cells to Increase the Efficacy of Doxorubicin.
| S-EPMC6014697 | biostudies-literature
Unknown Na/K-ATPase beta1-subunit associates with neuronal growth regulator 1 (NEGR1) to participate in intercellular interactions.
| S-EPMC8016658 | biostudies-literature
Unknown Methamphetamine and inflammatory cytokines increase neuronal Na+/K+-ATPase isoform 3: relevance for HIV associated neurocognitive disorders.
| S-EPMC3360751 | biostudies-literature