RT Journal Article
SR Electronic
T1 Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.03.498586
DO 10.1101/2022.07.03.498586
A1 Ulku Cuhadar
A1 Lorenzo Calzado-Reyes
A1 Carlos Pascual-Caro
A1 Aman S. Aberra
A1 Abhi Aggarwal
A1 Kaspar Podgorski
A1 Michael B. Hoppa
A1 Jaime de Juan-Sanz
YR 2022
UL http://biorxiv.org/content/early/2022/07/03/2022.07.03.498586.abstract
AB The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how the landscape of trans-synaptic bridges dynamically remodels to reflect functional states of the synapse. Here we developed novel optical tools to visualize in firing synapses the molecular behavior of a particular secreted trans-synaptic protein, LGI1, and its presynaptic receptor, ADAM23, and discovered that neuronal activity acutely rearranges the abundance of these proteins at the synaptic cleft. Surprisingly, LGI1 in synapses was not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23. Activity-driven translocation of LGI1 facilitated the formation of trans-synaptic connections proportionally to the history of activity of the synapse, modulating excitatory transmission correlatively to synaptic firing rates. Thus, our findings reveal that LGI1 abundance at the synaptic cleft can be acutely remodeled and serves as critical point of activity-dependent control of synaptic function.Highlights- Neuronal activity translocates LGI1 and ADAM23 to the presynaptic surface- LGI1 and ADAM23 are not located in synaptic vesicles- Stable cleft localization of LGI1 depends on the history of synaptic activity- LGI1 abundance at the synaptic cleft controls glutamate releaseCompeting Interest StatementThe authors have declared no competing interest.