Evolution of Na,K-ATPase βm-subunit into a coregulator of transcription in placental mammals

Pestov, Nikolay B.; Ahmad, Nisar; Korneenko, Tatyana V.; Zhao, Hao; Radkov, Rossen; Schaer, Danièle; Roy, Sophie; Bibert, Stéphanie; Geering, Käthi; Modyanov, Nikolaï N.

doi:10.1073/pnas.0704809104

Cited by 30 publications

(34 citation statements)

References 41 publications

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“…This likelihood is supported by findings that several NETs with unknown functions identified in the leukocyte data sets could alter genome organization 9 . More compelling, though, is the observation that even a protein with a known and distinct function identified in our data sets—the Na,K-ATPase βm-subunit—has been confirmed at the NE and found to serve a secondary function as a co-regulator of transcription 51 , 52 …”

Section: Discussionsupporting

confidence: 67%

The nuclear envelope proteome differs notably between tissues

Korfali

Wilkie

Swanson

et al. 2012

Nucleus

176

187

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One hypothesis to explain how mutations in the same nuclear envelope proteins yield pathologies focused in distinct tissues is that as yet unidentified tissue-specific partners mediate the disease pathologies. The nuclear envelope proteome was recently determined from leukocytes and muscle. Here the same methodology is applied to liver and a direct comparison of the liver, muscle and leukocyte data sets is presented. At least 74 novel transmembrane proteins identified in these studies have been directly confirmed at the nuclear envelope. Within this set, RT-PCR, western blot and staining of tissue cryosections confirms that the protein complement of the nuclear envelope is clearly distinct from one tissue to another. Bioinformatics reveals similar divergence between tissues across the larger data sets. For proteins acting in complexes according to interactome data, the whole complex often exhibited the same tissue-specificity. Other tissue-specific nuclear envelope proteins identified were known proteins with functions in signaling and gene regulation. The high tissue specificity in the nuclear envelope likely underlies the complex disease pathologies and argues that all organelle proteomes warrant re-examination in multiple tissues.

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Section: Discussionsupporting

confidence: 67%

The nuclear envelope proteome differs notably between tissues

Korfali

Wilkie

Swanson

et al. 2012

Nucleus

176

187

View full text Add to dashboard Cite

show abstract

“…Unfortunately, domain or family resemblances have little predictive value, since several validated NETs appear to be splice variants of proteins that function in the cytoplasm, mitochondria or plasma membrane. For example the Na,K-ATPase beta m subunit, which normally functions in a larger complex as a Na + /K + translocating ATPase at the surface of most cells, can also localize independently of the rest of the complex at the NE of neonatal skeletal muscle and C2C12 cells where it functions in transcriptional regulation [139]. Tissue-specific NETs may have arisen during evolution by amplification and adaptation of cytoplasmic proteins for secondary nuclear functions, as proposed [139]; alternatively, some ancestral proteins may have functioned at the NE as proposed for intermediate filaments [140].…”

Section: Future Outlookmentioning

confidence: 99%

“…For example the Na,K-ATPase beta m subunit, which normally functions in a larger complex as a Na + /K + translocating ATPase at the surface of most cells, can also localize independently of the rest of the complex at the NE of neonatal skeletal muscle and C2C12 cells where it functions in transcriptional regulation [139]. Tissue-specific NETs may have arisen during evolution by amplification and adaptation of cytoplasmic proteins for secondary nuclear functions, as proposed [139]; alternatively, some ancestral proteins may have functioned at the NE as proposed for intermediate filaments [140]. What is clear is that tissue-specificity of the NE arises in many ways and makes this organelle critical for integrating genome function in specific cell types.…”

Section: Future Outlookmentioning

confidence: 99%

Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

Worman

Schirmer

2015

Current Opinion in Cell Biology

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Human ‘laminopathy’ diseases result from mutations in genes encoding nuclear lamins or nuclear envelope (NE) transmembrane proteins (NETs). These diseases present a seeming paradox: the mutated proteins are widely expressed yet pathology is limited to specific tissues. New findings suggest tissue-specific pathologies arise because these widely expressed proteins act in various complexes that include tissue-specific components. Diverse mechanisms to achieve NE tissue-specificity include tissue-specific regulation of the expression, mRNA splicing, signaling, NE-localization and interactions of potentially hundreds of tissue-specific NETs. New findings suggest these NETs underlie tissue-specific NE roles in cytoskeletal mechanics, cell-cycle regulation, signaling, gene expression and genome organization. This view of the NE as ‘specialized’ in each cell type is important to understand the tissue-specific pathology of NE-linked diseases.

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“…The a subunit harbors the catalytic functions, whereas the b subunit is essential for stability and trafficking of the Na þ pump (for review see Blanco, 2005;Geering, 2008). In some tissues, an additional modulatory c unit, the FXYD protein, is associated with the a and b subunits (Geering, 2006;Pestov et al, 2007;Sweadner and Rael, 2000; for review see Geering, 2008), and recently the crystal structure of this oligomeric Na þ /K þ -ATPase was resolved (Morth et al, 2007). To accommodate the varying needs of different cell types and tissues, there exist multiple forms of the Na þ /K þ -ATPase providing the basis for the heterogeneity of the enzyme.…”

mentioning

confidence: 99%

Distribution of Na/K‐ATPase alpha 3 isoform, a sodium‐potassium P‐type pump associated with rapid‐onset of dystonia parkinsonism (RDP) in the adult mouse brain

Bøttger

Tracz

Heuck

et al. 2010

J of Comparative Neurology

141

134

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The Na(+)/K(+)-ATPase1 alpha subunit 3 (ATP1α(3)) is one of many essential components that maintain the sodium and potassium gradients across the plasma membrane in animal cells. Mutations in the ATP1A3 gene cause rapid-onset of dystonia parkinsonism (RDP), a rare movement disorder characterized by sudden onset of dystonic spasms and slowness of movement. To achieve a better understanding of the pathophysiology of the disease, we used immunohistochemical approaches to describe the regional and cellular distribution of ATP1α(3) in the adult mouse brain. Our results show that localization of ATP1α(3) is restricted to neurons, and it is expressed mostly in projections (fibers and punctuates), but cell body expression is also observed. We found high expression of ATP1α(3) in GABAergic neurons in all nuclei of the basal ganglia (striatum, globus pallidus, subthalamic nucleus, and substantia nigra), which is a key circuitry in the fine movement control. Several thalamic nuclei structures harboring connections to and from the cortex expressed high levels of the ATP1α(3) isoform. Other structures with high expression of ATP1α(3) included cerebellum, red nucleus, and several areas of the pons (reticulotegmental nucleus of pons). We also found high expression of ATP1α(3) in projections and cell bodies in hippocampus; most of these ATP1α(3)-positive cell bodies showed colocalization to GABAergic neurons. ATP1α(3) expression was not significant in the dopaminergic cells of substantia nigra. In conclusion, and based on our data, ATP1α(3) is widely expressed in neuronal populations but mainly in GABAergic neurons in areas and nuclei related to movement control, in agreement with RDP symptoms.

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Evolution of Na,K-ATPase βm-subunit into a coregulator of transcription in placental mammals

Cited by 30 publications

References 41 publications

The nuclear envelope proteome differs notably between tissues

The nuclear envelope proteome differs notably between tissues

Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

Distribution of Na/K‐ATPase alpha 3 isoform, a sodium‐potassium P‐type pump associated with rapid‐onset of dystonia parkinsonism (RDP) in the adult mouse brain

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