Project Details
Projekt
Autophagic regulation of synapse formation and maintenance
Applicant
Professor Dr. Peter Robin Hiesinger
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Cell Biology
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 447288260
Autophagy serves distinct local functions at developing and adult synaptic terminals. These functions rely on what substrates are engulfed and degraded in a time- and location-dependent manner, yet little is known about the substrate specificity of developmental autophagy versus autophagy at functional synapses. In RP7 we will investigate locally regulated autophagy at synaptic terminals compared to other cellular compartments in developing and adult neurons using photoreceptor neurons in the Drosophila brain as a model. This project is motivated by our recent discovery in these neurons that autophagosomes form selectively at the tips of synaptogenic filopodia during late brain development, thereby regulating synapse formation. What substrates underlie this process remains unknown. The identification of selective autophagy in the small space of a filopodial tip led us to hypothesize that the time and location of autophagosome formation may significantly restrict available substrates. This hypothesis provides an opportunity to test the general importance of restricted local substrate availability for spatiotemporally distinct roles of autophagy. We have therefore devised a substrate probe panel for comparative live imaging of local autophagy in collaboration with the entire Syntophagy consortium. In our first aim, we will use our established Drosophila brain culture multiphoton imaging system to live observe local substrate engulfment and degradation at developing and adult synaptic terminals, axons and cell bodies in wild type. The second aim is devised to utilize the same live imaging approach under conditions of decreased or increased autophagy levels. The third aim is devised to compare local autophagic roles to proteasomal and other endomembrane degradation pathways. Our first goal is to elucidate the mechanism of local autophagy during synapse formation. In addition, when these experiments are concluded we will have established a first comparative, substrate-focusedpicture of spatiotemporally distinct roles of autophagy in developing and functional neurons.
DFG Programme
Research Units
