TY - JOUR

T1 - Regulation of the synaptic vesicle liquid phase by dynamic SH3 domain binding

AU - Brodin, Lennart

AU - Sopova, E.

AU - Gerth, Fabian

AU - Freund, Christian

AU - Shupliakov, O.

PY - 2021/12

Y1 - 2021/12

N2 - Synaptic vesicle (SV) clusters are essential for neurotransmitter release at high rates of stimulation [1] with a role in pathological states, such as epilepsy. It was proposed that the resting SV cluster is organized as a liquid phase maintained by interactions of the intrinsically disordered region (IDR) of synapsin. To address how the SV liquid phase is regulated during synaptic activity we used intersectin (ITSN) as model protein. Intersectin, which is accumulated in the SV cluster, interacts with the synapsin IDR through a conserved phospho-regulated switch mechanism. In dephospho-intersectin, synapsin-binding to an ITSN SH3 domain is autoinhibited while in phospho-intersectin it strongly binds synapsin.

AB - Synaptic vesicle (SV) clusters are essential for neurotransmitter release at high rates of stimulation [1] with a role in pathological states, such as epilepsy. It was proposed that the resting SV cluster is organized as a liquid phase maintained by interactions of the intrinsically disordered region (IDR) of synapsin. To address how the SV liquid phase is regulated during synaptic activity we used intersectin (ITSN) as model protein. Intersectin, which is accumulated in the SV cluster, interacts with the synapsin IDR through a conserved phospho-regulated switch mechanism. In dephospho-intersectin, synapsin-binding to an ITSN SH3 domain is autoinhibited while in phospho-intersectin it strongly binds synapsin.

U2 - 10.1016/j.euroneuro.2021.10.269

DO - 10.1016/j.euroneuro.2021.10.269

M3 - Conference article

VL - 53

SP - S205

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - Supplement 1

Y2 - 2 October 2021 through 5 October 2021

ER -