Circadian Clock Regulation of the Secretory Pathway [article]

Ching-Yan Chloé Yeung, Richa Garva, Adam Pickard, Joan Chang, David F. Holmes, Yinhui Lu, Venkatesh Mallikarjun, Joe Swift, Antony Adamson, Ben Calverley, Qing Jun Meng, Karl E. Kadler
2018 bioRxiv   pre-print
Proteins destined for secretion move from the endoplasmic reticulum (ER, the site of synthesis) to Golgi cisternae then to the cell surface in transport vesicles. Although the mechanism of anterograde and retrograde transport via vesicles is well understood the temporal coordination of transport between organelles has not been studied. Here we show that the extracellular levels of collagen-I (the most abundant secreted protein in vertebrates) are rhythmic over a 24-hour cycle in tendon, the
more » ... ue richest in collagen-I. Rhythmicity is the result of circadian clock control of the secretory pathway via ER-ribosome docking, Tango1-dependent ER export, phosphodiesterase-dependent Golgi-ER retrograde transport of Hsp47 (a collagen molecular chaperone), and Vps33b-dependent post Golgi export. These mechanisms pause collagen-I transport at each node of the pathway over a 24-hour cycle. Thus, the circadian clock is a master logistic operator of the secretory pathway in mammalian cells.
doi:10.1101/304014 fatcat:z7ysg57qj5cttjga4i7kb3qvfm