Phospholemman expression induces a hyperpolarization-activated chloride current in Xenopus oocytes.

Moorman, J. Randall; Palmer, Cathy J.; John, J. Edward; Durieux, Marcel E.; Jones, Larry R.

doi:10.1016/s0021-9258(18)42074-1

Cited by 145 publications

(21 citation statements)

References 26 publications

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“…FXYD4 (corticosteroid hormone-induced factor; Attali et al, 1995 ) was also found in kidney, where its expression increases in response to corticosteroid hormone. FXYD1 (phospholemman; Palmer et al, 1991 ; Moorman et al, 1992 ) was found to be an important PKA and PKC protein target in the heart and skeletal muscle, and was later reported in brain and kidney ( Arystarkhova et al, 2017 ; Feschenko et al, 2003 ). FXYD6 (phosphohippolin) and FXYD7 seem to be exclusive to the nervous system ( Béguin et al, 2002 ; Delprat et al, 2007 ; Kadowaki et al, 2004 ), while FXYD3 (Mat-8; Morrison et al, 1995 ) and FXYD5 (dysadherin or related to ion channel; Ino et al, 2002 ) are expressed in several epithelia and appear to be up-regulated in certain cancers.…”

Section: Introductionmentioning

confidence: 99%

FXYD protein isoforms differentially modulate human Na/K pump function

Meyer

Sautu

Spontarelli

et al. 2020

Journal of General Physiology

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Tight regulation of the Na/K pump is essential for cellular function because this heteromeric protein builds and maintains the electrochemical gradients for Na+ and K+ that energize electrical signaling and secondary active transport. We studied the regulation of the ubiquitous human α1β1 pump isoform by five human FXYD proteins normally located in muscle, kidney, and neurons. The function of Na/K pump α1β1 expressed in Xenopus oocytes with or without FXYD isoforms was evaluated using two-electrode voltage clamp and patch clamp. Through evaluation of the partial reactions in the absence of K+ but presence of Na+ in the external milieu, we demonstrate that each FXYD subunit alters the equilibrium between E1P(3Na) and E2P, the phosphorylated conformations with Na+ occluded and free from Na+, respectively, thereby altering the apparent affinity for Na+. This modification of Na+ interaction shapes the small effects of FXYD proteins on the apparent affinity for external K+ at physiological Na+. FXYD6 distinctively accelerated both the Na+-deocclusion and the pump-turnover rates. All FXYD isoforms altered the apparent affinity for intracellular Na+ in patches, an effect that was observed only in the presence of intracellular K+. Therefore, FXYD proteins alter the selectivity of the pump for intracellular ions, an effect that could be due to the altered equilibrium between E1 and E2, the two major pump conformations, and/or to small changes in ion affinities that are exacerbated when both ions are present. Lastly, we observed a drastic reduction of Na/K pump surface expression when it was coexpressed with FXYD1 or FXYD6, with the former being relieved by injection of PKA's catalytic subunit into the oocyte. Our results indicate that a prominent effect of FXYD1 and FXYD6, and plausibly other FXYDs, is the regulation of Na/K pump trafficking.

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Section: Introductionmentioning

confidence: 99%

FXYD protein isoforms differentially modulate human Na/K pump function

Meyer

Sautu

Spontarelli

et al. 2020

Journal of General Physiology

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“…In addition to modulating NKA kinetics, our recent study showed FXYD6 drastically reduced plasma membrane functional expression of α1β1 in Xenopus oocytes ( Meyer et al, 2020 ), suggesting this protein may also function as a regulator of NKA localization to the plasma membrane. This is reminiscent of studies that showed that PLM phosphorylation ( Bibert et al, 2008 ; Meyer et al, 2020 ; Moorman et al, 1992 ) and palmitoylation ( Hilgemann et al, 2013 ) modulate NKA trafficking. The recent observations contribute to the emerging picture that FXYD proteins have important roles beyond simple regulation of NKA’s affinity for transported ions.…”

Section: Introductionmentioning

confidence: 81%

FXYD proteins and sodium pump regulatory mechanisms

Yap

Šeflová

Sweazey

et al. 2021

Journal of General Physiology

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The sodium/potassium-ATPase (NKA) is the enzyme that establishes gradients of sodium and potassium across the plasma membrane. NKA activity is tightly regulated for different physiological contexts through interactions with single-span transmembrane peptides, the FXYD proteins. This diverse family of regulators has in common a domain containing a Phe-X-Tyr-Asp (FXYD) motif, two conserved glycines, and one serine residue. In humans, there are seven tissue-specific FXYD proteins that differentially modulate NKA kinetics as appropriate for each system, providing dynamic responsiveness to changing physiological conditions. Our understanding of how FXYD proteins contribute to homeostasis has benefitted from recent advances described in this review: biochemical and biophysical studies have provided insight into regulatory mechanisms, genetic models have uncovered remarkable complexity of FXYD function in integrated physiological systems, new posttranslational modifications have been identified, high-resolution structural studies have revealed new details of the regulatory interaction with NKA, and new clinical correlations have been uncovered. In this review, we address the structural determinants of diverse FXYD functions and the special roles of FXYDs in various physiological systems. We also discuss the possible roles of FXYDs in protein trafficking and regulation of non-NKA targets.

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“…is among the smallest proteins known to form a membrane ion channel with expression observed in skeletal and heart muscle 6 . Injection of Xenopus oocytes with FXYD1 results in development of a chloride-selective current, featuring a sigmoidal delay and pulsed amplitude increase 7 . A central function of FXYD1 is in the regulation of the Na,K-ATPase (NKA); FXYD1 directly interacts with NKA -isoenzymes.…”

Section: Fxyd1 a Polypeptide 72 Amino Acids In Length (Also Known As Phospholemman [Plm])mentioning

confidence: 99%

FXYD1 is differentially expressed in non-small cell lung adenocarcinomas.

Mamoor¹

2020

Preprint

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Non-small cell lung adenocarcinoma (NSCLC) is a leading cause of death in the United States and worldwide (1, 2). We mined published microarray data (3, 4, 5) to discover genes associated with NSCLC. We identified significant differential expression of the FXYD domain-containing ion transport regulator 1 FXYD1 (6) in tumors from patients with NSCLC. FXYD1 may be of relevance to the initiation, progression or maintenance of non-small cell lung cancers.

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Phospholemman expression induces a hyperpolarization-activated chloride current in Xenopus oocytes.

Cited by 145 publications

References 26 publications

FXYD protein isoforms differentially modulate human Na/K pump function

FXYD protein isoforms differentially modulate human Na/K pump function

FXYD proteins and sodium pump regulatory mechanisms

FXYD1 is differentially expressed in non-small cell lung adenocarcinomas.

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