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SUMMARY:Procollagen quality control at ER exit sites  - Dr Shakib Omari\; 
 National Institute of Child Health &amp\; Human Development (NICHD)\, Rock
 ville\, Maryland\, USA
DTSTART:20190731T140000Z
DTEND:20190731T150000Z
UID:TALK127093@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Type I collagen is the main component of bone and other connec
 tive tissues. Defects in procollagen folding\, trafficking and degradation
  are key factors in bone and connective tissue pathologies. Autophagy has 
 been identified as the degradation pathway for misfolded procollagen that 
 avoids activation of generic ER-stress responses\; however\, the mechanism
  by which this occurs is unclear. To address this question\, we used live 
 cell and correlative light-electron microscopy (CLEM) imaging of procollag
 en with a Gly610-to-Cys substitution in mouse osteoblasts. This substituti
 on mimics a mouse model of bone pathology that involves autophagic degrada
 tion of misfolded mutant procollagen. Cells expressing fluorescently tagge
 d proteins confirmed that some dynamic procollagen puncta (~500nm) departe
 d from ER exit sites (ERESs) and traveled on to Golgi whereas other puncta
  co-localized with autophagic structures. These two fractions of procollag
 en represent the secretory compartment and the degradative compartment\, r
 espectively. Although procollagen vesicular traffic departing ERESs lacked
  components of the COPII coat (proteins associated with ER exit site forma
 tion)\, procollagen autophagic puncta colocalized with these ERES componen
 ts\, but not with ER lumen or membrane proteins. Moreover\, when ERES form
 ation was inhibited procollagen autophagic puncta decreased. This suggests
  that the rerouting of misfolded procollagen to autophagy occurs at ERESs.
  Further analyses\, including CLEM\, revealed that this delivery occurred 
 via a non-traditional form of autophagy known as microautophagy\, involvin
 g lysosomal engulfment of autophagic LC3-labeled ERESs containing misfolde
 d procollagen. Our current studies focus on the mechanisms involved in the
  sorting of folded vs misfolded procollagen at the level of the ERES.
LOCATION:Babraham - The Cambridge Building - Kings Hedges Room
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