Correlation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.

ABSTRACT:

Background

Pathogenic missense variants in the essential synaptic vesicle protein synaptotagmin-1 (SYT1) cause a neurodevelopmental disorder characterised by motor delay and intellectual disability, hyperkinetic movement disorder, episodic agitation, and visual impairments. SYT1 is the presynaptic calcium sensor that triggers synchronous neurotransmitter release. We have previously shown that pathogenic variants around the calcium-sensing region of the critical C2B domain decrease synaptic vesicle exocytosis in neurons.

Methods

Here, we have used cultured hippocampal neurons transfected with SYT1-pHluorin to examine how variants within the C2A and C2B domain of SYT1 impact evoked exocytosis.

Findings

We show that recently identified variants within the facilitatory C2

SUBMITTER: Park PY 

PROVIDER: S-EPMC11564929 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature