Deafness causing neuroplastin missense variants fail to promote plasma membrane Ca-ATPase levels and Ca transient regulation in brain neurons.

Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular levels.

Lysine 117 Residue Is Essential for the Function of the Hepatocyte Nuclear Factor 1α.

Unlabelled: Hepatocyte nuclear factor 1α (HNF1α) plays essential roles in controlling development and metabolism; its mutations are clearly linked to the occurrence of maturity-onset diabetes of the young (MODY3) in humans. Lysine 117 (K117) to glutamic acid (E117) mutation in the HNF1α gene has been clinically associated with MODY3, but no functional data on this variant are available. Here, we addressed the role of lysine 117 in HNF1α function using a knock-in animal model and site-directed mutagenesis.

Protective Role of Hepassocin against Hepatic Endoplasmic Reticulum Stress in Mice.

Hepassocin (HPS) is a hepatokine that has multiple proposed physiological functions. Some of the biological processes in which it is involved are closely related to endoplasmic reticulum (ER) stress, but the role of HPS in the regulation of ER stress remains unclear. Here, we demonstrated that transcription is induced by the protein kinase RNA-like ER kinase (PERK)/activating transcription factor 4 (ATF4) cascade upon ER stress in hepatocytes.

HPS protects the liver against steatosis, cell death, inflammation, and fibrosis in mice with steatohepatitis.

Hepassocin (HPS) is a hepatokine associated with metabolic regulation and development of non-alcoholic steatohepatitis (NASH). However, previous reports on HPS are controversial and its true function is not yet understood. Here, we demonstrated that hepatic HPS expression levels were upregulated in short-term feeding and downregulated in long-term feeding in high-fat diet (HFD)- and methionine- and choline-deficient (MCD) diet-fed mice, as well as in genetically obese (ob/ob) mice.