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SUMMARY:Exploring new roles for ER-mitochondria organelle contacts in neur
 ons - Professor Franck Polleux | Columbia University 
DTSTART:20190411T140000Z
DTEND:20190411T150000Z
UID:TALK121843@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:Interfaces between organelles\, such as ER and mitochondria\, 
 are emerging as critical platforms for many biological responses in eukary
 otic cells. However\, the function of ER-mitochondria coupling in developi
 ng and adult neurons is currently unknown despite recent ultrastructural e
 vidence (including our own results) showing that numerous direct contacts 
 between ER and mitochondria can be observed in dendrites in vivo. In addit
 ion\, changes in the extent of ER-mitochondria contacts have been reported
  in various models of neurodegenerative diseases such as Alzheimer’s dis
 ease and Parkinson’s disease. To date\, the pathophysiological impact of
  these changes in ER-mitochondria contacts is largely unknown.\nI will giv
 e an update on our project aimed at exploring the role of ER-mitochondria 
 interface in neuronal development\, synaptic integration and circuit funct
 ion. The major roadblock to study the function of ER-mitochondria coupling
  in any cell types including neurons is due to the absence of a molecular 
 toolkit required to manipulate this organelle interface. We recently ident
 ified Pdzd8 as an ER protein playing a critical role in ER-mitochondria te
 thering (Hirabaryashi et al. Science 2017). We found that in cortical neur
 ons\, PDZD8 is required for Ca2+ uptake by mitochondria following synaptic
 ally-induced Ca2+-release from ER and thereby regulates cytoplasmic Ca2+ d
 ynamics in dendrites. Our results identify PDZD8 as the first\, critical E
 R- mitochondria tethering protein in metazoan cells and uncover a novel ro
 le for ER-mitochondria coupling in the regulation of dendritic Ca2+ dynami
 cs in mammalian neurons. We hypothesize that PDZD8-dependent ER-mitochondr
 ia tethering plays critical roles in regulating cytoplasmic Ca2+ homeostas
 is in dendrites and might contribute to the formation of branch-specific C
 a2+ ‘domains’ regulating synaptic integration and therefore in the den
 dritic properties underlying circuit function. We are currently testing th
 e role of ER-mitochondria contact\, in dendritic Ca2+ dynamics\, synaptic 
 integration and circuit function in vivo
LOCATION:Sackler Lecture Theatre (Level 7) Wellcome Trust/MRC Building\, C
 ambridge Biomedical Campus
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