Related Experiment Video

Updated: Jul 7, 2026

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Cotransporters, WNKs and hypertension: an update

Peter W Flatman1

  • 1Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. peter.flatman@ed.ac.uk

Current Opinion in Nephrology and Hypertension
|February 16, 2008
PubMed
Abstract

Insights

The With No Lysine (WNK) signalling cascade regulates blood pressure by controlling sodium transport. Aberrant WNK signalling increases sodium retention and vascular resistance, contributing to hypertension.

Area of Science:

  • Nephrology
  • Cardiovascular Physiology
  • Molecular Biology

Background:

  • The With No Lysine (WNK) signalling cascade is crucial for blood pressure regulation.
  • Dysregulation of this cascade is implicated in essential hypertension.
  • Key components include WNK kinases, SPAK/OSR1, and Cation-Chloride Cotransporters (CCCs).

Purpose of the Study:

  • To review the molecular interactions within the WNK-SPAK/OSR1-CCC signalling cascade.
  • To elucidate the role of this cascade in sodium homeostasis and hypertension pathogenesis.
  • To explore the impact of WNK mutations on blood pressure regulation.

Main Methods:

  • Review of studies involving transgenic animals and gene knockins.
  • Analysis of functional studies on WNK1 phosphorylation and activity.
  • Examination of structural data on SPAK/OSR1 interactions.

Main Results:

  • Mutant WNK4 increases kidney sodium-chloride cotransporter (NCC) expression and activity.
  • WNK1 phosphorylation regulates its activity and interaction with SPAK/OSR1.
  • The structural basis for SPAK/OSR1 target interactions has been elucidated.

Conclusions:

  • WNKs activate SPAK/OSR1, which phosphorylates and activates NCCs and Na-K-Cl cotransporters (NKCCs).
  • This leads to increased sodium retention and vascular resistance, contributing to hypertension.
  • Hypertension-associated WNK mutants enhance renal tubular NKCC2 and NCC activity, though their full role requires further investigation.

More Related Videos

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies07:10

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies

Published on: September 29, 2023

Related Concept Videos

Transcellular Transport of Solutes01:23

Transcellular Transport of Solutes

Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
Nonlinear Pharmacokinetics: Role of Transporters01:27

Nonlinear Pharmacokinetics: Role of Transporters

A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
Active Transport01:14

Active Transport

Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...