Project Details
Projekt
Amphisome biogenesis, trafficking and signaling at presynaptic boutons.
Applicants
Anna Karpova, Ph.D.; Dr. Michael R. Kreutz
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 447288260
There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. Emphasizing the need to understand autophagic function at the synapse, autophagic dysfunction has been reported in neurodevelopmental disorders that are thought to arise from synaptic deficits. An intriguing possibility that has not been investigated in detail is whether and how autophagy directly contributes to activity-dependent synaptic change. Unfortunately, it is currently unknown whether autophagy has a specific role in synaptic neurotransmission that goes beyond protein degradation and whether endosomal sorting processes and removal of membrane proteins at boutons actively contribute to synaptic plasticity. In support of this latter notion several recent studies suggest that different membrane sources and mechanisms might underlie phagophore formation in a stimulus-dependent manner. In this project we will try to understand whether the assembly of amphisomes at boutons is involved in presynaptic plasticity and long-range signaling. Autophagosomes fuse with late endosomes in order to undergo robust retrograde transport and we hypothesize that in the absence of autolysosome formation, the resulting amphisomes serve as signaling and sorting platforms while trafficking in a retrograde direction to the cell soma. This could give an answer to questions such as why neurons transport autophagic and endocytic cargos back to the cell body for degradation instead of disposing them locally, how signaling endosomes escape a degradative pathway following endocytosis and how autophagy regulates presynaptic plasticity. Our overarching hypothesis is that the enormous complexity of neuronal cytoarchitecture has led to ways of long-distance protein transport that combine degradative with signaling functions.
DFG Programme
Research Units
