Evidence for an interaction between adducin and Na+-K+-ATPase

Relation to genetic hypertension

Mara Ferrandi, Sergio Salardi, Grazia Tripodi, Paolo Barassi, Rodolfo Rivera, Paolo Manunta, Rivka Goldshleger, Patrizia Ferrari, Giuseppe Bianchi, Steven J D Karlish

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Adducin point mutations are associated with genetic hypertension in Milan hypertensive strain (MHS) rats and in humans. In transfected cells, adducin affects actin cytoskeleton organization and increases the Na+-K+- pump rate. The present study has investigated whether rat and human adducin polymorphisms differently modulate rat renal Na+-K+ATPase in vitro. We report the following. 1) Both rat and human adducins stimulate Na+-K+- ATPase activity, with apparent affinity in tens of nanomolar concentrations. 2) MHS and Milan normotensive strain (MNS) adducins raise the apparent ATP affinity for Na+-K+-ATPase. 3) The mechanism of action of adducin appears to involve a selective acceleration of the rate of the conformational change E2 (K)- E1 (Na) or E2(K). ATP → E1Na·ATP. 4) Apparent affinities for mutant rat and human adducins are significantly higher than those for wild types. 5) Recombinant human α- and β-adducins stimulate Na+-K+-ATPase activity, as do the COOH-terminal tails, and the mutant proteins display higher affinities than the wild types. 6) The cytoskeletal protein ankyrin, which is known to bind to Na+-K+-ATPase, also stimulates enzyme activity, whereas BSA is without effect; the effects of adducin and ankyrin when acting together are not additive. 7) Pig kidney medulla microsomes appear to contain endogenous adducin; in contrast with purified pig kidney Na+-K+ATPase, which does not contain adducin, added adducin stimulates the Na+-K+-ATPase activity of microsomes only about one-half as much as that of purified Na+- K+-ATPase. Our findings strongly imply the existence of a direct and specific interaction between adducin and Na+-K+-ATPase in vitro and also suggest the possibility of such an interaction in intact renal membranes.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number4 46-4
Publication statusPublished - Oct 1999

Fingerprint

Hypertension
Ankyrins
Microsomes
Kidney
adducin
sodium-translocating ATPase
Swine
Adenosine Triphosphate
Kidney Medulla
Cytoskeletal Proteins
Mutant Proteins
Actin Cytoskeleton
Point Mutation
Tail
Membranes
Enzymes

Keywords

  • Blood pressure
  • Cytoskeleton
  • Genetics

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Evidence for an interaction between adducin and Na+-K+-ATPase : Relation to genetic hypertension. / Ferrandi, Mara; Salardi, Sergio; Tripodi, Grazia; Barassi, Paolo; Rivera, Rodolfo; Manunta, Paolo; Goldshleger, Rivka; Ferrari, Patrizia; Bianchi, Giuseppe; Karlish, Steven J D.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 277, No. 4 46-4, 10.1999.

Research output: Contribution to journalArticle

Ferrandi, M, Salardi, S, Tripodi, G, Barassi, P, Rivera, R, Manunta, P, Goldshleger, R, Ferrari, P, Bianchi, G & Karlish, SJD 1999, 'Evidence for an interaction between adducin and Na+-K+-ATPase: Relation to genetic hypertension', American Journal of Physiology - Heart and Circulatory Physiology, vol. 277, no. 4 46-4.
Ferrandi, Mara ; Salardi, Sergio ; Tripodi, Grazia ; Barassi, Paolo ; Rivera, Rodolfo ; Manunta, Paolo ; Goldshleger, Rivka ; Ferrari, Patrizia ; Bianchi, Giuseppe ; Karlish, Steven J D. / Evidence for an interaction between adducin and Na+-K+-ATPase : Relation to genetic hypertension. In: American Journal of Physiology - Heart and Circulatory Physiology. 1999 ; Vol. 277, No. 4 46-4.
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AU - Barassi, Paolo

AU - Rivera, Rodolfo

AU - Manunta, Paolo

AU - Goldshleger, Rivka

AU - Ferrari, Patrizia

AU - Bianchi, Giuseppe

AU - Karlish, Steven J D

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