Summary
This project aims to identify and investigate novel intracellular proteins, specifically p130Cas, that determine the distinct nanoscopic architecture of Neurexin-1 and Neurexin-3 at synapses, which is crucial for efficient synaptic communication.
What they want
The project will use orthogonal 3D STED and 3D dSTORM imaging to dissect how p130Cas regulates neurexin-1 and the nanoarchitecture of excitatory synapses (Aim 1). Additionally, classic structure-function approaches will be employed to define the sequences necessary and sufficient for p130Cas and neurexin-1 binding, and electrophysiology will assess the functional implications of these interactions (Aim 2). The research builds on preliminary data indicating p130Cas controls neurexin-1 surface expression, nanocluster volume, and presynaptic release probability.
Deliverables
- First critical insight into how neurexin nanoclusters (NCs) are established
- Definition of how individual Neurexins (Nrxns) differentially control intracellular signaling
- A methodological framework to interrogate other candidate proteins
Technical requirements
- 3D dSTORM super-resolution imaging
- Double epitope-tag mouse line
- Immunolabeling of Nrxn1 and Nrxn3
- Co-immunoprecipitation mass spectrometry
- 3D STED imaging
- Structure-function approaches
- Electrophysiology
