<i>Dnajc22</i> - a new susceptibility gene for salt-sensitive hypertension

Abstract

Chaperones of the heat shock (HSP) 70 family mediate elementary funtions in a cell, such as folding, oligomerization, transport, or degradation of proteins. Their function is particularly needed when cells are exposed to straining conditions such as heat stress or an overloading of the protein translation machinery. To carry out their function HSP70 proteins need cochaperones of the J protein family, which stimulate the ATPase activity of HSP70 proteins by their J domain. <br /><i>Dnajc22</i> is an evolutionary conserved member of the J protein family, bearing a single ortholog in fruit fly, zebrafish, mouse, and human. No functional data on its role in mammalian physiology had been published before.<br /> The generation of <i>Dnajc22</i>-deficient mice revealed that the murine protein is not essential for development and survival of the organism. In fact, its function is needed when the organism has to cope with slightly more stressful conditions. After receiving a diet containing elevated sodium chloride concentrations, analyses revealed that mice lacking <i>Dnajc22</i> are not able to cope with the challenge as well as their wildtype littermates, as they show abnormal electrolyte handling and differences in peripheral blood pressure measurements. Further experiments showed that <i>Dnajc22</i> is part of the osmotic stress response of the cell. <br /> The findings of this work show for the first time, that mammalian <i>Dnajc22</i> is needed to deal with osmotically straining conditions on an cellular as well as organismal level.