Electrochemical Monitoring of Real‐Time Vesicle Dynamics Induced by Tau in a Confined Nanopipette

The microtubule‐associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau‘s engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an elect...

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Veröffentlicht in:Angewandte Chemie International Edition 2024-09, Vol.63 (39), p.e202406677-n/a
Hauptverfasser: Chen, Ke‐Le, Yu, Ru‐Jia, Zhong, Cheng‐Bing, Wang, Ziyi, Xie, Bao‐Kang, Ma, Hui, Ao, Mingjun, Zheng, Peng, Ewing, Andrew G., Long, Yi‐Tao
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Sprache:eng
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Zusammenfassung:The microtubule‐associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau‘s engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse‐mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid‐modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p‐tau) present two‐state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid‐tau interaction. The results indicate that p‐tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease. We developed a synapse‐mimicking nanopipette method to electrochemically monitor single vesicle dynamics induced by lipid‐tau interactions. Characteristic ionic current oscillations have been used to evaluate the binding affinity, indicating that phosphorylated tau inhibits vesicle dynamics through strong interactions with synaptic vesicles. This finding sheds light on the mechanism of vesicle‐mediated tau spreading and tau pathology.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202406677