Randall K. Wetzel
Harvard University
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Featured researches published by Randall K. Wetzel.
Journal of Biological Chemistry | 1999
Elena Arystarkhova; Randall K. Wetzel; Natalya K. Asinovski; Kathleen J. Sweadner
The Na+,K+-ATPase catalyzes the active transport of ions. It has two necessary subunits, α and β, but in kidney it is also associated with a 7.4-kDa protein, the γ subunit. Stable transfection was used to determine the effect of γ on Na,K-ATPase properties. When isolated from either kidney or transfected cells, αβγ had lower affinities for both Na+ and K+ than αβ. A post-translational modification of γ selectively eliminated the effect on Na+ affinity, suggesting three configurations (αβ, αβγ, and αβγ*) conferring different stable properties to Na,K-ATPase. In the nephron, segment-specific differences in Na+ affinity have been reported that cannot be explained by the known α and β subunit isoforms of Na,K-ATPase. Immunofluorescence was used to detect γ in rat renal cortex. Cortical ascending limb and some cortical collecting tubules lacked γ, correlating with higher Na+ affinities in those segments reported in the literature. Selective expression in different segments of the nephron is consistent with a modulatory role for the γ subunit in renal physiology.
Annals of the New York Academy of Sciences | 2003
Kathleen J. Sweadner; Elena Arystarkhova; Claudia Donnet; Randall K. Wetzel
Abstract: The FXYD gene family has seven members in mammals and others in fish. Five of these (FXYD1, FXYD2, FXYD4, FXYD7, and PLMS from shark) have been shown to alter the activity of the Na,K‐ATPase, as described by other papers in this volume. The gene structure of FXYD family members suggests assembly from protein domain modules and gene duplication. The γ subunit is unique in the family for having alternative splice variants in the coding region and can be posttranslationally modified with different final consequences for enzyme properties. The nonoverlapping distribution of γ and CHIF (FXYD4) in kidney helps to explain physiological differences in Na+ affinity among nephron segments. We also detected phospholemman (FXYD1) in kidney. By immunofluorescence, it was found in extraglomerular mesangial cells (EM cells) of the juxtaglomerular apparatus and in the afferent arteriole. Contrary to many reports that only α1 and β1 are expressed in the kidney, we found that α2 and β2 are present, although not in any nephron segment. Both were detected in arterioles, and β2 was found in the EM cells. In contrast, α1, β1, and γ were found in adjacent macula densa. Phospholemman, α2, and β2 are proposed to have distinct roles in regulating the sodium pump in structures involved in tubuloglomerular feedback.
Glia | 2000
Pablo Martín-Vasallo; Randall K. Wetzel; Luis Miguel Garcia-Segura; Eduardo Molina-Holgado; Elena Arystarkhova; Kathleen J. Sweadner
The Na,K‐ATPase, which catalyzes the active transport of Na+ and K+, has two principal subunits (α and β) that have several genetically distinct isoforms. Most of these isoforms are expressed in the nervous system, but certain ones are preferentially expressed in glia and others in neurons. Of the β isoforms, β1 predominates in neurons and β2 in astrocytes, although there are some exceptions. Here we demonstrate that β3 is expressed in rat and mouse white matter oligodendrocytes. Immunofluorescence microscopy identified β3 in oligodendrocytes of rat brain white matter in typical linear arrays of cell bodies between fascicles of axons. The intensity of stain peaked at 20 postnatal days. β3 was identified in cortical oligodendrocytes grown in culture, where it was expressed in processes and colocalized with antibody to galactocerebroside. In the mouse and rat optic nerve, β3 stain was seen in oligodendrocytes, where it colocalized with carbonic anhydrase II. For comparison, optic nerve was stained for the β1 and β2 subunits, showing distinct patterns of labelling of axons (β1) and astrocytes (β2). The C6 glioma cell line was also found to express the β3 isoform preferentially. Since β3 was not found at detectable levels in astrocytes, this suggests that C6 is closer to oligodendrocytes than astrocytes in the glial cell lineage. GLIA 31:206–218, 2000.
Annals of the New York Academy of Sciences | 2003
Elena Arystarkhova; Randall K. Wetzel
Abstract: Renal Na,K‐ATPase is tightly bound to a small regulatory protein, the gamma subunit (FXYD2). In rat, it occurs in two splice variants with different N‐termini. Immunolocalization on kidney sections revealed distinct distribution of the γ splice variants along the rat nephron. Where coexpressed, they coimmunoprecipitated with each other along with the alpha subunit, suggesting assembly in oligomeric complexes. Functional consequences of association with gamma were monitored in stably transfected NRK‐52E cells. The outcome was that splice variants can differentially modulate the major intrinsic properties of the Na,K‐ATPase under normal and stress‐related conditions. The data imply an adaptive physiological mechanism of regulation of renal Na,K‐ATPase through modulation of pump properties, gene expression, or both.
The Journal of Neuroscience | 2003
Marina S. Feschenko; Claudia Donnet; Randall K. Wetzel; Natalya K. Asinovski; Larry R. Jones; Kathleen J. Sweadner
The Journal of Neuroscience | 1999
Randall K. Wetzel; Elena Arystarkhova; Kathleen J. Sweadner
American Journal of Physiology-renal Physiology | 2002
Elena Arystarkhova; Randall K. Wetzel; Kathleen J. Sweadner
American Journal of Physiology-renal Physiology | 2001
Randall K. Wetzel; Kathleen J. Sweadner
Biochemical and Biophysical Research Communications | 2000
Kathleen J. Sweadner; Randall K. Wetzel; Elena Arystarkhova
Journal of Biological Chemistry | 2004
Randall K. Wetzel; Jennifer L. Pascoa; Elena Arystarkhova