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Event Type:  Seminar (This is an NIH Science event)
Annual Lecture:  Other
Title:  New insights into secretory pathway protein quality control revealed by monitoring the fate of misfolded GPI-anchored proteins
Description:  The accumulation of misfolded secretory pathway proteins may result in disruptive and toxic molecular interactions, such as those associated with prion and Alzheimer’s diseases. Accordingly, cells have evolved multiple protein quality control (QC) pathways to recognize misfolded secretory pathway proteins in the endoplasmic reticulum (ER) and promote their clearance. The best characterized clearance pathways for misfolded secretory pathway proteins are ER associated degradation or autophagy, both of which act at the ER. However, there is a growing appreciation that some misfolded secretory pathway proteins constitutively escape degradation at the ER and traverse the secretory pathway before being handled by downstream QC pathways. For example, misfolding mutants of a prevalent class of membrane proteins called glycosylphosphatidylinositol-anchored proteins (GPI-APs), which includes prion disease-associated mutants of PrP, are transferred from the ER resident chaperone, calnexin, to the ER export factor, Tmp21, for vesicular export. This pathway is enhanced by ER stress. We named this ER export pathway RESET (for rapid ER stress-enhanced export). Upon release from the ER, the misfolded GPI-APs move through the Golgi and briefly access the plasma membrane before being internalized for lysosomal degradation. Knockdown of Tmp21 not only prevents RESET of misfolded GPI-APs, but also can lead to their aggregation in the ER. Recently, we discovered that a subset of misfolded transmembrane proteins, including some mutants of LDLR and APP, associate with Tmp21 and are cleared from the ER by RESET. Our discovery of Tmp21’s role in RESET is especially intriguing in light of recent discoveries by other labs that misregulation of Tmp21 is connected to amyloidogenesis and Alzheimer’s disease. We are now dissecting the precise role of Tmp21 in the QC of misfolded secretory pathway proteins. Additionally, we are characterizing the currently unknown QC system(s) that target and send
Series Name:  Neurons, Brains and Behavior is a seminar series organized by NIH postdocs
Videocast:  Event will not be videocast
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Wednesday, February 28, 2018   11:00am - 12:00pm Add To Outlook Calendar     Add To iCal Calendar     Add To Entourage Calendar
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Name:   Prasanna Satpute-Krishnan, PhD
Title:   Assistant Professor
Organization:   Department of Biochemistry and Molecular Biology Uniformed Services Un
City/Province:   Bethesda,
State:   Maryland
Country:   USA

Organization(s):  [NIH] National Institute of Neurological Disorders and Stroke (NINDS)

Location:  On the main NIH Campus
Building:  Building 35
Room:  Room 610
Street Address:  35 Convent Dr
City:  Bethesda
State:  Maryland
Zip Code:  20814

Name:   Richa Lomash
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