Abstract:

Neurons largely lack Golgi apparatuses within their processes, yet the cellular machinery supporting secretion of locally translated proteins remains poorly defined. In non-neuronal cells, recent studies have implicated autophagosomes - classically degradative organelles - in the trafficking of cargoes to the plasma membrane (PM). However, whether secretory autophagy operates in neurons under basal conditions has remained unclear. In this seminar, I will present our work identifying secretory autophagosomes in neuronal processes, defined by co-expression of LC3 and the vesicular SNARE SEC22B. By combining immunopurification of these vesicles from brain tissue with proteomic profiling, we find that they are enriched in soluble and integral membrane proteins, including numerous proteins with established synaptic functions. Using a function-blocking nanobody against SEC22B, we have also developed a specific approach to inhibit secretory autophagy, with functional and behavioural consequences following its application in vivo. Together, these findings establish secretory autophagy as a contributor to type III Golgi-bypass secretion in neurons. They identify a non-canonical role for autophagosomes in shaping the synaptic surfaceome and reveal an additional layer to the autophagic regulation of synaptic proteostasis and function.

Bio:

Erin studied Biomedical Sciences at Cardiff University, including a professional research-training year in the laboratory of Prof. Alun Davies, FRS. She remained at Cardiff and completed a PhD in Neurobiology with Prof. Yves-Alain Barde, where she validated a GFP reporter mouse model to study endogenous Bdnf expression in the rodent brain. Since joining the University of Lausanne as a postdoctoral fellow in 2021, Erin has led work on how autophagy-related protein trafficking shapes the neuronal surface and synaptic proteostasis within brain. Her research combines neuronal and mouse models with quantitative proteomics, protein biochemistry, organelle immunopurification and multiscale imaging to define the mechanisms maintaining the synaptic and surface proteome.