Keeping the Synapse in Shape: Local Protein Removal
Brain function relies on neurotransmission at synapses, where fast increases in calcium trigger the fusion of synaptic vesicles and release of their neurotransmitters. Synapses maintain their molecular composition and function through the concerted action of protein synthesis and degradation. Our research group aims to understand how old, dysfunctional synaptic components are removed to keep synapses functional over long periods of time.
The Organization and Function of the Neuronal ER
Membrane trafficking events and local organelles contribute to synapse functioning. The neuronal endoplasmic reticulum (ER) extends for hundreds of microns as a huge network throughout the highly branched neurites and even into synapses. ER tubules serve important functions in regulating membrane proteins, lipids and Ca2+ levels. Despite the importance of this huge organelle and its involvement in a range of neurodegenerative diseases, we know little about how the tubular ER, and its associated proteins, contributes to neuron development and neurotransmission.
Fundamental information on mechanisms of intracellular degradation and organelle organization will not only help us to understand how individual synapses work, it may also lead to insights on the role of these particular processes in neurodegenerative diseases that involve ER or proteostasis dysfunction.
