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We are pleased to present Dr. Merja Joensuu to speak on Botulinum neurotoxin type A hijacks a heterotrimeric plasma membrane complex to intoxicate neurons.

When: Thursday 3rd August 2023

Where: AIBN Level 1 Seminar room or online viz zoom. Click here to join

The title: Botulinum neurotoxin type A hijacks a heterotrimeric plasma membrane complex to intoxicate neurons.


Abstract: The unique nerve terminal targeting of botulinum neurotoxin type A (BoNT/A), one of the most toxic compounds known to date, is due to its capacity to bind 2 receptors on the neuronal plasma membrane: polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). How PSGs and SV2 coordinate BoNT/A binding and internalization has remained unknown. Using live-cell super-resolution imaging and electron microscopy of catalytically inactivated BoNT/A wildtype and receptor-binding-deficient mutants in cultured neurons, we recently demonstrated that the targeted endocytosis of BoNT/A into synaptic vesicles (SVs), which is a requisite for the toxin-induced neuroparalysis, requires a coordination of a heterotrimeric complex on the neuronal plasma membrane. Coincidental binding of BoNT/A to a preassembled PSG-synaptotagmin-1 (Syt1) complex and SV2 on the neuronal plasma membrane facilitates Syt1-SV2 nanoclustering which, in turn, controls endocytic sorting of the toxin into SVs. Syt1 CRISPRi knockdown limits both BoNT/A- and BoNT/E-induced neurointoxication, suggesting that this heterotrimeric complex may be a general neurointoxication strategy for several botulinum neurotoxin serotypes.


Bio: Dr Merja Joensuu obtained her PhD in biochemistry from the University of Helsinki, Finland, in 2014. Her postdoctoral training at the Queensland Brain Institute, The University of Queensland, was supported by the Academy of Finland postdoctoral fellowship and ARC DECRA, and she is the recipient of several project grants. She was appointed as a UQ Amplify Fellow at the Australian Institute for Bioengineering and Nanotechnology and Queensland Brain Institute, The University of Queensland, mid 2022, where she leads her own research laboratory. Her laboratory uses advanced imaging techniques such as live cell super-resolution imaging and high-resolution electron microscopy, and a range of cell biological techniques, to understand the molecular mechanisms regulating cellular membrane dynamics, aiming to discover novel therapeutic strategies for the treatment of genetic diseases, viral infections and neurointoxication pathologies.



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