Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission

Ulku Cuhadar, Lorenzo Calzado-Reyes, Carlos Pascual-Caro, Aman S. Aberra, Andreas Ritzau-Jost, Abhi Aggarwal, Keiji Ibata, Kaspar Podgorski, Michisuke Yuzaki, Christian Geis, Stefan Hallerman, Michael B. Hoppa, Jaime de Juan-Sanz

研究成果: Article査読

抄録

The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how trans-synaptic bridges change to reflect the functional states of the synapse. Here, we develop optical tools to visualize in firing synapses the molecular behavior of two trans-synaptic proteins, LGI1 and ADAM23, and find that neuronal activity acutely rearranges their abundance at the synaptic cleft. Surprisingly, synaptic LGI1 is primarily not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23. Activity-driven translocation of LGI1 facilitates the formation of trans-synaptic connections proportionally to the history of activity of the synapse, adjusting excitatory transmission to synaptic firing rates. Accordingly, we find that patient-derived autoantibodies against LGI1 reduce its surface fraction and cause increased glutamate release. Our findings suggest that LGI1 abundance at the synaptic cleft can be acutely remodeled and serves as a critical control point for synaptic function.

本文言語English
論文番号114186
ジャーナルCell Reports
43
5
DOI
出版ステータスPublished - 2024 5月 28

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学一般

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