Circadian control of the secretory pathway maintains collagen homeostasis
Collagen is the most abundant secreted protein in vertebrates and persists throughout life without renewal. The permanency of collagen networks contrasts with continued collagen synthesis throughout adulthood and with conventional transcriptional/translational homeostatic mechanisms that replace damaged proteins with new copies. Here we show circadian clock regulation of ER-to-plasma membrane procollagen transport by sequential rhythmic expression of SEC61, TANGO1, PDE4D and VPS33B. The result is nocturnal procollagen synthesis and daytime collagen fibril assembly in mice. Rhythmic collagen degradation by CTSK maintains collagen homeostasis. This circadian cycle of collagen synthesis and degradation affects a pool of newly-synthesised collagen whilst maintaining the persistent collagen network. Disabling the circadian clock causes abnormal collagen fibrils and collagen accumulation which is reduced in vitro by NR1D1 and CRY1/2 agonists SR9009 and KL001, respectively. In conclusion, our study has identified a circadian clock mechanism of protein homeostasis wherein a sacrificial pool of collagen maintains tissue function.
Date: 15 October 2021, 13:00 (Friday, 1st week, Michaelmas 2021)
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: The Blakemore Lecture Theatre
Speaker: Professor Karl Kadler (University of Manchester)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organisers: Dr Adam Packer (University of Oxford), Associate Professor Duncan Sparrow (DPAG, University of Oxford)
Organiser contact email address:
Host: Professor Paul Riley (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Talitha Smith