Dynamic Na/H exchanger 1 (NHE1) - calmodulin complexes of varying stoichiometry and structure regulate Ca-dependent NHE1 activation.

Calmodulin (CaM) engages in Ca-dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction with the human Na/H-exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, and fibroblasts stably expressing wildtype and mutant NHE1, we discovered multiple accessible states of this functionally important complex existing in different NHE1:CaM stoichiometries and structures. We determined the NMR solution structure of a ternary complex in which CaM links two NHE1 cytosolic tails.

The intracellular lipid-binding domain of human Na/H exchanger 1 forms a lipid-protein co-structure essential for activity.

Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na/H-exchanger 1 (NHE1) regulates intracellular pH (pH) with dysregulation linked to e.g.

Ex vivo effect of hemostatic therapy in subarachnoid and intracerebral hemorrhage.

Background: Rebleeding and hematoma growth are serious complications in subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). As treatment options are sparse, a mechanistic approach may reveal new therapeutic targets.

Aim: Firstly, to evaluate hemostasis using a sensitive low tissue factor thromboelastometry (ROTEM®) assay in patients with SAH or ICH and compare them with healthy controls.