QBI Neuroscience Seminar: 'A highly Munc18-ocentric Hitchhiker's Guide to the Galaxy'

Event Details

Date:

Wednesday, 04 April 2018 - Wednesday, 04 April 2018

Time:

11:00 am - 12:00 pm

Room:

QBI Level 7 Auditorium

UQ Location:

Queensland Brain Institute (St Lucia)

URL:

http://www.qbi.uq.edu.au/neuroscience-seminars

Event category(s):

Full Description:: YeJin Chai
Queensland Brain Institute, University of Queensland
Title: 'A highly Munc18-ocentric Hitchhiker's Guide to the Galaxy'
Abstract:
Neurons communicate through the release of neurotransmitter stored in synaptic vesicles located in nerve terminals. Several key molecules such as STXBP1 (also known as Munc18-1) and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) control the exocytic fusion of these vesicles with the plasma membrane. Deletion of Munc18-1 not only block neurotransmitter release but also leads to widespread neurodegeneration through unknown mechanism. Munc18-1 de novo heterozygous mutations cause developmental defects and epileptic phenotypes including early infantile epileptic encephalopathy type 4 (EIEE4). The mechanism by which these mutations lead to this pathology is poorly understood, and may involve either haploinsufficiency and/or a gain of pathological function of the mutant allele. In this talk, I will present our recent discoveries suggesting that Munc18-1 human EIEE4 mutants confer a gain of toxic function via protein aggregation-induced neurodegeneration. Furthermore, I will show how the nanoscale organization of Munc18-1 is altered by Munc18-1 EIEE-causing mutant in neurosecretory cells and hippocampal neurons using single-molecule imaging.