Research identifies novel intracellular pathway important for collagen homeostasis

A collaboration between researchers at UCL, led by BRC-funded Professor Paul Gissen, has identified a novel intracellular pathway important for generic collagen homeostasis. Furthermore, this pathway was found to be dependent on two proteins that are defective in Arthrogryposis Renal dysfunction and Cholestasis (ARC) syndrome.

Findings showed that regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and the development and function of multiple organs and tissues. This pathway was found to be dependent on the protein VIPAR and its partner proteins. These findings were confirmed in patients with ARC.

ARC syndrome is a multisystem disorder, characterised by defects of the musculoskeletal system and LH3-specific collagen modification levels are reduced in these patients. Findings showed functional collagen abnormalities in cells and tissues of these patients, which are caused by VIPAR and VPS33B deficiencies, suggesting that these deficiencies result in abnormal LH3-dependent post-translational modification of collagen in these patients. Furthermore, Kevin Mills’ laboratory, funded by the BRC discovered urine biomarkers that will allow easy and early diagnosis in these patients which could help avoid unnecessary investigations.

Findings have been published in Nature Communications.