ePoster

Characterisation of Magi-family synaptic scaffolding proteins in human iPSC-derived neurons

Maximilian Borgmeyer, Julia Knocks, Tomas Fanutza, Lukas Einhäupl, Doris Lau, Christian Wozny, Nina Wittemayer
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Maximilian Borgmeyer, Julia Knocks, Tomas Fanutza, Lukas Einhäupl, Doris Lau, Christian Wozny, Nina Wittemayer

Abstract

Synapse formation is critical for the wiring of neural circuits in the developing brain. The composition and function of synapses has predominantly been studied in rodent cells. Here we show a novel protocol to generate human iPSC-derived forebrain-like neurons that show rapid synaptic development. To achieve this, we use an astrocyte feeder layer attached to a complex mix of ECM-components. Neuronal stem cells (NCS) are plated on this layer for maturation into neurons. We use this protocol to provide an initial characterisation of Magi-family synaptic scaffolding proteins in human neurons. Both Magi1 and Magi2 are expressed in the brain, however expression levels of Magi-2 are much higher in neurons than in any other cell type, while Magi-1 is expressed more evenly throughout cell types and tissues. In rodents the synaptic scaffolding protein S-SCAM/Magi-2 plays a critical role in the assembly and maintenance of synapses and interacts with signalling proteins facilitating synapse to nucleus signalling. Increased expression of S-SCAM/Magi-2 in the human brain is associated with schizophrenia. We show that Magi-1 can be found at both inhibitory and excitatory synapses in human neurons and can substitute for the loss of Magi-2. Lastly, we analyse how S-SCAM/Magi-2 levels at the synapse influences gene expression, via synapse to nucleus signalling.

Unique ID: fens-24/characterisation-magi-family-synaptic-ac63886d