CHEVI complex in collagen homeostasis
|Dates:||13 November 2017|
|Times:||13:00 - 14:00|
|What is it:||Seminar|
|Organiser:||Faculty of Biology, Medicine and Health|
|Who is it for:||University staff, Current University students|
Athrogryposis, Renal Dysfunction and Cholestasis syndrome (ARC) is an autosomal recessive multisystem disorder caused by deficiencies of VPS33B and VIPAR (Gissen et al, 2004, Cullinane et al, 2010). ARC affects the function of kidneys, liver, bones and blood cells (Gissen et al, 2006). There is a scope of severity with most severely affected patients dying in the first year of life, whilst patients with mild mutations live into adulthood (Smith et al, 2012, Gruber et al, 2017). There are no available disease modifying therapies in ARC.
Recent work from ours and other labs suggested that VPS33B and VIPAR form a protein complex CHEVI which is essential for biogenesis of specialised intracellular organelles in various tissue types. So far, CHEVI’s role has been linked with the biogenesis of platelet alpha granules, keratinocyte lamellar bodies and pattern recognition receptor (PRR) carrying endosomes in immune cells (Bem et al, 2015, Gruber et al, 2017, Akbar et al, 2016, Rogerson et al, 2016). We discovered that CHEVI is necessary for the delivery of collagen processing enzymes such LH3 into newly described collagen IV carrier or "CIVC" in mouse kidney collecting duct cells (Banushi et al, 2016). We found that abnormal CIVC formation due to CHEVI defects was associated with Collagen IV structural and functional defects, disruption of cell polarity and mechanical properties of tissues.
Organisation: MRC Laboratory for Molecular Cell Biology, UCL
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