Mutation of a conserved proline residue in the β-subunit ectodomain prevents Na+-K+-ATPase oligomerization

K. Geering, P. Jaunin, F. Jaisser, A. M. Merillat, J. D. Horisberger, P. M. Mathews, Mario Victor Lemas, D. M. Fambrough, B. C. Rossier

Research output: Contribution to journalArticle

Abstract

A highly conserved sequence motif (4 tyrosines and 1 proline: YYPYY) of the Na+-K+-adenosinetriphosphatase (ATPase) β1-subunit ectodomain has been mutagenized to study its possible role in α/β-assembly and sodium pump function. Single as well as double tyrosine mutants (tyrosine to phenylalanine: Y to F) of Xenopus laevis β1-subunits are able to associate with α1-subunits and form functional Na-K pumps at the plasma membrane that are indistinguishable from wild-type α11-Na-K pumps (as assessed by measurements of ouabain binding, 86Rb flux, Na-K pump current, and activation by external potassium). In contrast, a single proline mutation (proline to glycine: P244G) reduced by >90% the proper assembly and function of Na+-K+-ATPase, despite a normal rate of synthesis and core glycosylation. Our data indicate that proline-244 plays a critical role in the proper folding of the β-subunit and its ability to associate efficiently with the α1-subunit in the endoplasmic reticulum.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume265
Issue number4 34-4
StatePublished - 1993
Externally publishedYes

Fingerprint

Oligomerization
Proline
Adenosine Triphosphatases
Tyrosine
Mutation
Pumps
Glycosylation
Sodium-Potassium-Exchanging ATPase
Conserved Sequence
Xenopus laevis
Ouabain
Cell membranes
Phenylalanine
Endoplasmic Reticulum
Glycine
Potassium
Chemical activation
Cell Membrane
Fluxes

Keywords

  • α-subunit
  • functional expression
  • oocyte
  • potassium activation
  • sodium pump
  • sodium-potassium-adenosinetriphosphatase
  • Xenopus laevis

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Geering, K., Jaunin, P., Jaisser, F., Merillat, A. M., Horisberger, J. D., Mathews, P. M., ... Rossier, B. C. (1993). Mutation of a conserved proline residue in the β-subunit ectodomain prevents Na+-K+-ATPase oligomerization. American Journal of Physiology - Cell Physiology, 265(4 34-4).

Mutation of a conserved proline residue in the β-subunit ectodomain prevents Na+-K+-ATPase oligomerization. / Geering, K.; Jaunin, P.; Jaisser, F.; Merillat, A. M.; Horisberger, J. D.; Mathews, P. M.; Lemas, Mario Victor; Fambrough, D. M.; Rossier, B. C.

In: American Journal of Physiology - Cell Physiology, Vol. 265, No. 4 34-4, 1993.

Research output: Contribution to journalArticle

Geering, K, Jaunin, P, Jaisser, F, Merillat, AM, Horisberger, JD, Mathews, PM, Lemas, MV, Fambrough, DM & Rossier, BC 1993, 'Mutation of a conserved proline residue in the β-subunit ectodomain prevents Na+-K+-ATPase oligomerization', American Journal of Physiology - Cell Physiology, vol. 265, no. 4 34-4.
Geering, K. ; Jaunin, P. ; Jaisser, F. ; Merillat, A. M. ; Horisberger, J. D. ; Mathews, P. M. ; Lemas, Mario Victor ; Fambrough, D. M. ; Rossier, B. C. / Mutation of a conserved proline residue in the β-subunit ectodomain prevents Na+-K+-ATPase oligomerization. In: American Journal of Physiology - Cell Physiology. 1993 ; Vol. 265, No. 4 34-4.
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abstract = "A highly conserved sequence motif (4 tyrosines and 1 proline: YYPYY) of the Na+-K+-adenosinetriphosphatase (ATPase) β1-subunit ectodomain has been mutagenized to study its possible role in α/β-assembly and sodium pump function. Single as well as double tyrosine mutants (tyrosine to phenylalanine: Y to F) of Xenopus laevis β1-subunits are able to associate with α1-subunits and form functional Na-K pumps at the plasma membrane that are indistinguishable from wild-type α1,β1-Na-K pumps (as assessed by measurements of ouabain binding, 86Rb flux, Na-K pump current, and activation by external potassium). In contrast, a single proline mutation (proline to glycine: P244G) reduced by >90{\%} the proper assembly and function of Na+-K+-ATPase, despite a normal rate of synthesis and core glycosylation. Our data indicate that proline-244 plays a critical role in the proper folding of the β-subunit and its ability to associate efficiently with the α1-subunit in the endoplasmic reticulum.",
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AU - Horisberger, J. D.

AU - Mathews, P. M.

AU - Lemas, Mario Victor

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AU - Rossier, B. C.

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