Developmental Causes of Focal Segmental Glomerulosclerosis.

Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS.

Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture.

The Copper Metabolism MURR1 domain protein 1 (COMMD1) modulates the aggregation of misfolded protein species in a client-specific manner.

The Copper Metabolism MURR1 domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and hypoxia signalling. Acting as a scaffold protein, COMMD1 mediates the levels, stability and proteolysis of its substrates (e.g.

D-serine influences synaptogenesis in a p19 cell model.

Recently, D-serine has been identified as an important NMDA-receptor co-agonist, which might play a role in central nervous system development. We investigated this by studying rat P19 cells, an established model for neuronal and glial differentiation. Our results show that (1) the D-serine synthesizing enzyme serine racemase was expressed upon differentiation, (2) extracellular D-serine concentrations increased upon differentiation, which was inhibited by serine racemase antagonism, and (3) inhibition of D-serine synthesis or prevention of D-serine binding to the NMDA-receptor increased synaptophysin expression and intercellular connections, supporting a role for NMDA-receptor activation by D-serine, synthesized by serine racemase, in shaping synaptogenesis and neuronal circuitry during central nervous system development.

Monitoring bile acid transport in single living cells using a genetically encoded Förster resonance energy transfer sensor.

Unlabelled: Bile acids are pivotal for the absorption of dietary lipids and vitamins and function as important signaling molecules in metabolism. Here, we describe a genetically encoded fluorescent bile acid sensor (BAS) that allows for spatiotemporal monitoring of bile acid transport in single living cells. Changes in concentration of multiple physiological and pathophysiological bile acid species were detected as robust changes in Förster resonance energy transfer (FRET) in a range of cell types.

Liver-specific Commd1 knockout mice are susceptible to hepatic copper accumulation.

Canine copper toxicosis is an autosomal recessive disorder characterized by hepatic copper accumulation resulting in liver fibrosis and eventually cirrhosis. We have identified COMMD1 as the gene underlying copper toxicosis in Bedlington terriers. Although recent studies suggest that COMMD1 regulates hepatic copper export via an interaction with the Wilson disease protein ATP7B, its importance in hepatic copper homeostasis is ill-defined.