MONaKA, a Novel Modulator of the Plasma Membrane Na,K-ATPase

Mao, Hua; Ferguson, Tanya S; Cibulsky, Susan M.; Holmqvist, Mats; Ding, Chunming; Fu, Hong; Levitan, Irwin B.

doi:10.1523/jneurosci.0635-05.2005

Cited by 27 publications

(21 citation statements)

References 38 publications

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“…PXK encodes a multimodular protein composed of a phox homology domain, a protein kinase-like domain, and a WiskottAldrich syndrome protein homology 2 domain. The gene product of PXK regulates the activity of Na-ATPase and K-ATPase ion transport, and is expressed in the kidney (57,58). Recent data suggest that PXK has a critical role in trafficking of the EGF receptor through modulation of ligandinduced ubiquitination of the receptor.…”

Section: Discussionmentioning

confidence: 99%

Association of Systemic Lupus Erythematosus Susceptibility Genes with IgA Nephropathy in a Chinese Cohort

Zhou

Cheng

Zhu

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives One hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls.Design, setting, participants, & measurements This study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population.

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Section: Discussionmentioning

confidence: 99%

Association of Systemic Lupus Erythematosus Susceptibility Genes with IgA Nephropathy in a Chinese Cohort

Zhou

Cheng

Zhu

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Zou et al reported that there were five splice variants of the human PXK gene with different subcellular localization (75), and Mao et al showed that PXK, designated MONaKA (modulator of Na,K-ATPase), modulated the activity of the Na,K- ATPase, as assessed by catalytic activity and functional ion transport activity, by directly interacting with the ␤-subunit (45). The ubiquitous tissue distribution of PXK, analyzed by Northern blotting and Western blotting in this study, correlated with the results obtained by reverse transcription-PCR analyses in those reports.…”

Section: Discussionmentioning

confidence: 99%

“…The following primers were used for PCR: F1, 5Ј-GCAAGGTGCTGCT GGACGACAC-3Ј; F2, 5Ј-AGCCAAAGTGGGAGGTGGTGGAAC-3Ј; R1, 5Ј-ACTTGTCTGGGCCAAGGTCAGC-3Ј; and R2, TCAAGGTCCAGCAGC-CGGCAAG-3Ј. PCR was performed with F1/R1, F1/R2, and F2/R2 primer sets to detect several splice variants of PXK (45), and the reaction with each combination of primers gave a single band.…”

Section: Methodsmentioning

confidence: 99%

Characterization of PXK as a Protein Involved in Epidermal Growth Factor Receptor Trafficking

Takeuchi

Gao

et al. 2010

Molecular and Cellular Biology

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The phox homology (PX) domain is a phosphoinositide-binding module that typically binds phosphatidylinositol 3-phosphate. Out of 47 mammalian proteins containing PX domains, more than 30 are denoted sorting nexins and several of these have been implicated in internalization of cell surface proteins to the endosome, where phosphatidylinositol-3-phosphate is concentrated. Here we investigated a multimodular protein termed PXK, composed of a PX domain, a protein kinase-like domain, and a WASP homology 2 domain. We show that the PX domain of PXK localizes this protein to the endosomal membrane via binding to phosphatidylinositol 3-phosphate. PXK expression in COS7 cells accelerated the ligand-induced internalization and degradation of epidermal growth factor receptors by a mechanism requiring phosphatidylinositol 3-phosphate binding but not involving the WASP homology 2 domain. Conversely, depletion of PXK using RNA interference decreased the rate of epidermal growth factor receptor internalization and degradation. Ubiquitination of epidermal growth factor receptor by the ligand stimulation was enhanced in PXK-expressing cells. These results indicate that PXK plays a critical role in epidermal growth factor receptor trafficking through modulating ligand-induced ubiquitination of the receptor.Both constitutive endocytosis and activated endocytosis are highly regulated events by which cells take up nutrients and internalize receptors for recycling or degradation (47). Endocytosed molecules are delivered to early endosomes, where the components are sorted to the cell surface for recycling back to the plasma membrane, or to late endosomes to be degraded in lysosomes (17). The molecular mechanisms regulating these events are not fully understood.One of the major protein families involved in the trafficking of membrane compartments is sorting nexins (SNXs), which are characterized by the presence of phox homology (PX) domains (8,65). The PX domain is a protein module which consists of approximately 130 amino acids with three ␤-strands followed by three ␣-helices forming a helical subdomain, and the general function of this module is to interact with the head groups of inositol phospholipids through which parental proteins are targeted to specific cellular compartments. Most of the SNXs examined to date specifically recognize phosphatidylinositol 3-phosphate [PtdIns(3)P], which is found predominately in early endosomes (11). The founding member of the SNX family, SNX1, was initially identified as an interaction partner of epidermal growth factor receptor (EGFR), and the expression of SNX1 enhanced lysosomal degradation of EGFR (38); therefore, SNXs are most likely to be involved in the trafficking of many different families of receptors which are recycled to the cell surface or sent to the lysosome for degradation (19). On the other hand, PX domain-containing proteins have also been reported to bind to phosphoinositides other than PtdIns(3)P and to have functions independent of receptor trafficking (54). For example, phosp...

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“…The 3p14 region with suggestive evidence for linkage harbors candidate genes such as: FEZF2 (3p14.2), which regulates the specification of corticospinal motor neurons and sub-cerebral projection neurons [Molyneaux et al, 2007] may also be involved in innate immunity; CADPS (3p14.2), expressed in brain, neural and endocrine-specific tissue, which encodes a calcium-binding membrane protein essential for exocytosis of vesicles filled with neurotransmitters and neuropeptides [Binda et al, 2005]; SYNPR (3p14.2), isolated from brain, which encodes a membrane protein of synaptic vesicles and up-regulation was noted upon peripheral nerve injury [Sun et al, 2006]; ABHD6 (3p14.3), which codes a brain enzyme that has been implicated in endocannabinoid signaling [Blankman et al, 2007]; PXK (3p14.3), whose functions include cell communication and regulation of synaptic transmission [Mao et al, 2005;Zhang et al, 2009]; KCTD6 (3p14.3), which involved in voltage-gated potassium channel activity; and ACOX2 (3p14.3), which is implicated in neurodevelopmental delay and brain dysfunction [Wanders and Waterham, 2006].…”

Section: Discussionmentioning

confidence: 99%

A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12

Butler

Breen

Tozzi

et al. 2010

American J of Med Genetics Pt B

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Suicidal behavior is commonly associated with depression. Twin studies indicate that both suicidality and major depressive disorder (MDD) are heritable. However, epidemiological evidence suggests that the inheritance of suicidality is likely to be independent of the underlying psychiatric disorder, implying a distinct genetic contribution to suicidality. We conducted a genomewide linkage search aiming to detect genomic loci that may harbor susceptibility genes contributing to risk for suicidality in recurrent MDD. Affected sibling pair (ASP) variance components analysis was performed using the Depression Network cohort of 971 ASPs. The quantitative trait measuring suicidality as a broad phenotype, encompassing ideation and suicide attempts, was established from Schedules for Clinical Assessment in Neuropsychiatry interview items. We examined 1,060 genotyped microsatellite markers with an average spacing of 3.3 cM. Empirical thresholds for linkage evidence were set by whole-genome simulations (LOD = 2.71 for genomewide significance, 1.71 for suggestive linkage). No genomewide significant findings were found. Marker D3S1234 on 3p14 achieved suggestive linkage and yielded a maximum LOD of 1.853 (P = 0.0017), loci 9p24.3 and 18q22-q23 achieved LOD scores >1.5. We found some support for linkage to 2p12 (LOD = 1.2, P = 0.0087) which was previously implicated in linkage studies of suicidality. Our follow-up meta-analysis of five studies showed strong linkage to this region (P = 2 × 10(-6) ). In conclusion, this study analyzed suicidality as a continuous trait in MDD. We found modest evidence for linkage on 3p14. Our meta-analysis supports previous evidence of linkage to suicidality on 2p12. Some candidate genes in these regions may plausibly be implicated in suicidality. © 2010 Wiley-Liss, Inc.

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MONaKA, a Novel Modulator of the Plasma Membrane Na,K-ATPase

Cited by 27 publications

References 38 publications

Association of Systemic Lupus Erythematosus Susceptibility Genes with IgA Nephropathy in a Chinese Cohort

Association of Systemic Lupus Erythematosus Susceptibility Genes with IgA Nephropathy in a Chinese Cohort

Characterization of PXK as a Protein Involved in Epidermal Growth Factor Receptor Trafficking

A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12

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