The proteome of gap junctions

  Learn more on our team's website here.

  Contact Mario DE BONO at mario.debono@ist.ac.at

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NERVSPAN project

Neurons communicate via two kinds of synapses, chemical and electrical. Electrical synapses connect the cytoplasm of two cells and allow passage of ions and small molecules. Gap junctions can be quite large (in the order of 100s of nm), appear to be highly dynamic, and can show long-term potentiation. Biochemical studies suggest that electrical synapses, like chemical synapses, are complex assemblages of proteins. We know relatively little about how gap junctions age, but multiple lines of evidence implicate ageing-related gap junction defects in a range of human pathologies.

Gap junctions represent about a quarter of synaptic connections in C. elegans. This project proposes to combine biochemical, cell biological and genetic studies to probe how gap junctions change with ageing in the nematode.

Objectives

In this project you will:

• tag different innexins with TurboID and compare the proteomes associated with them as animals age;
• •validate changes in gap junction compositions using fluorescent labelling in vivo in select neurons;
• functionally probe how ageing alters gap junctions.

We will employ: cell-specific labeling of gap junctions, and cell-specific (and time-selective) knockdown of molecules associated with ageing synapses. The auxin-inducible degron system will be used to study how such molecules contribute to gap junction function. We will also seek to use Ca²⁺ imaging to report on the functionality of gap junctions, focusing in particular on a hub-and-spoke circuit that mediates escape from 21% O₂ and where gap junctional connectivity appears to play a prominent role.