QBI Neuroscience Seminar: “Activity-dependent bulk endocytosis: presynaptic function and dysfunction in Huntington’s Disease”
Event Details
- Date:
- Tuesday, 23 January 2018 - Tuesday, 23 January 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):
Event Contact
- Name:
- Ms Deirdre Wilson
- Phone:
- 3346 6300
- Email:
- d.wilson5@uq.edu.au
- Org. Unit:
- Queensland Brain Institute
Event Description
- Full Description:
- Professor Mike Cousin, Chair of Neuronal Cell Biology, Centre for Integrative Physiology,
University of Edinburgh, Edinburgh, Scotland
Title: “Activity-dependent bulk endocytosis: presynaptic function and dysfunction in Huntington’s Disease”
Abstract: The coordinated recruitment and integration of presynaptic synaptic vesicle (SV) recycling modes is a key factor in maintaining synaptic transmission during elevated neuronal activity. During periods of high neuronal activity, activity-dependent bulk endocytosis (ADBE) is the dominant mode, which retrieves large areas of membrane directly forming bulk endosomes from which SVs can bud. We have identified the first ADBE-specific SV cargo, called VAMP4, and have shown that it is essential for ADBE to proceed. In addition to a key role in neuronal physiology ADBE dysfunction may precipitate a series of neuronal disorders that rely on high frequency neurotransmission. One such disorder is Huntington’s disease (HD), which is caused by mutation of the HTT gene, with synaptic atrophy prevalent in striatal medium spiny neurons. We tested whether this vulnerability originates from an inability to sustain presynaptic performance during intense neuronal activity. Two distinct activity-dependent signatures of presynaptic dysfunction were revealed in neurons derived from a HD mouse model. First, ADBE was increased in neurons derived from different brain regions. Second, clathrin-mediated endocytosis was disrupted specifically in striatal neurons and only during elevated activity. Loss of wild-type huntingtin function precipitated these disease signatures, since both were recapitulated by depletion of endogenous huntingtin from wild-type neurons. Importantly both disease signatures were eliminated by overexpression of wild-type huntingtin in HD neurons. Intrinsic susceptibility of specific HD neurons to elevated neuronal activity via ADBE dysfunction may therefore render them vulnerable to ongoing physiological firing patterns, potentially explaining synapse failure and degeneration in later life.
Directions to UQ
- Google Map:
-
- Directions:
- St Lucia Campus | Gatton campus.
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