McQuillan Molly

No Thumbnail Available
Last Name
McQuillan
First Name
Molly
ORCID
0000-0001-7062-8379

Filters

2020 - 2023 2
2
2
Reset filters

Settings

Search Results

Now showing 1 - 2 of 2
  • Article
    Hsc70 ameliorates the vesicle recycling defects caused by excess alpha-synuclein at synapses
    (Society for Neuroscience, 2020-01-15) Banks, Susan M. L. ; Medeiros, Audrey T. ; McQuillan, Molly ; Busch, David J. ; Ibarraran-Viniegra, Ana Sofia ; Sousa, Rui ; Lafer, Eileen M. ; Morgan, Jennifer R.
    α-Synuclein overexpression and aggregation are linked to Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and several other neurodegenerative disorders. In addition to effects in the cell body, α-synuclein accumulation occurs at presynapses where the protein is normally localized. While it is generally agreed that excess α-synuclein impairs synaptic vesicle trafficking, the underlying mechanisms are unknown. We show here that acute introduction of excess human α-synuclein at a classic vertebrate synapse, the lamprey reticulospinal (RS) synapse, selectively impaired the uncoating of clathrin-coated vesicles (CCVs) during synaptic vesicle recycling, leading to an increase in endocytic intermediates and a severe depletion of synaptic vesicles. Furthermore, human α-synuclein and lamprey γ-synuclein both interact in vitro with Hsc70, the chaperone protein that uncoats CCVs at synapses. After introducing excess α-synuclein, Hsc70 availability was reduced at stimulated synapses, suggesting Hsc70 sequestration as a possible mechanism underlying the synaptic vesicle trafficking defects. In support of this hypothesis, increasing the levels of exogenous Hsc70 along with α-synuclein ameliorated the CCV uncoating and vesicle recycling defects. These experiments identify a reduction in Hsc70 availability at synapses, and consequently its function, as the mechanism by which α-synuclein induces synaptic vesicle recycling defects. To our knowledge, this is the first report of a viable chaperone-based strategy for reversing the synaptic vesicle trafficking defects associated with excess α-synuclein, which may be of value for improving synaptic function in PD and other synuclein-linked diseases.
  • Article
    Hsc70 rescues the synaptic vesicle trafficking defects caused by α-synuclein dimers
    (Caltech Library, 2023-03-01) Brady, Emily B ; McQuillan, Molly ; Medeiros, Audrey T ; Bubacco, Luigi ; Sousa, Rui ; Lafer, Eileen M ; Morgan, Jennifer R
    Aberrant buildup of α-synuclein is associated with Parkinson's disease (PD) and other neurodegenerative disorders. At synapses, α-synuclein accumulation leads to severe synaptic vesicle trafficking defects. We previously demonstrated that different molecular species of α-synuclein produce distinct effects on synaptic vesicle recycling, and that the synaptic phenotypes caused by monomeric α-synuclein were ameliorated by Hsc70. Here, we tested whether Hsc70 could also correct synaptic deficits induced by α-synuclein dimers. Indeed, co-injection of Hsc70 with α-synuclein dimers completely reversed the synaptic deficits, resulting in synapses with normal appearance. This work lends additional support for pursuing chaperone-based strategies to treat PD and other synucleinopathies.