Project Details
Projekt
Unveiling spatiotemporal dynamics and unconventional functions of the axonal autophagy–lysosomal system.
Applicant
Professorin Dr. Marina Mikhaylova
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 447288260
The autophagy-lysosomal system plays a central role in synaptic remodeling, but the exactmechanisms, which allow for tight spatio-temporal control of degradative organelle localizationand activity, are still poorly understood. In neurons, secretory-trafficking organelles frequentlygain new identities and adopt new cellular functions. Autophagosomes, formed in distal axonalcompartments need to be transported towards the soma where they fuse with lysosomes todegrade their content. During retrograde trafficking some autophagosomes fuse with lateendosomes to form transient organelles called amphisomes, which serve as signalingplatforms travelling from one synapse to the other. Similarly, only a fraction of endo-lysosomalorganelles in the axon are functional lysosomes and a large number of diverse intermediateshave other non-degrative roles. The local availability of degradation-competent lysosomes islikely one of the rate-limiting factors controlling the transformation of autophagosomes intoautolysosomes. With this project, we want to understand the processes involved inautophagosomal and lysosomal maturation in axons. We hypothesize that trafficking ofautophagosomal and endo-lysosomal organelles, dependent on the coordinated interplay ofactin and microtubule motor proteins, is essential for the timing of organelle’s transitions andthe location where these transitions might happen. Furthermore, we aim to addressunconventional roles of the endo-lysosomal and autophagy systems at the pre-synapse byinvestigating exocytosis as a mechanism responsible for a rapid clearance of ‘aged’ synapticcomponents.
DFG Programme
Research Units
