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The molecular mechanisms of clustered synaptic plasticity: focus on lysosomes

Subject Area Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2014 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 259979908
 
Final Report Year 2022

Final Report Abstract

The central aim of this research proposal is to test the hypothesis whether lysosomal positioning and exocytosis in dendrites plays a role in the establishment of clustered synaptic plasticity. This project builds up on the previous work performed in frame of the DFG Emmy Noether Program where we discovered new specialisations of dendritic actin cytoskeleton and showed that in principal neurons dense F-actin mesh surrounding excitatory shaft synapses served as a place for docking various secretory trafficking organelles. Thus, we could demonstrate that dendritic endolysosomes stall at the shaft synapses and that activation of actin motor myosin V leads to a long-term anchoring of the organelles. Here, we asked what is such lysosome positioning good for? In search for the answer, we explored non-conventional functions of neuronal lysosomes, such as exocytosis and control of dendritic mRNA translation. The preliminary data generated during implementation of this project led to two successful grant applications: a project within the newly funded DFG research unit 5228 “Membrane trafficking processes underlying presynaptic proteostasis” (project PI) and a project within the 2nd funding period of the DFG collaborative Research Center 1315 “Mechanisms and Disturbances in Memory Consolidation: From Synapses to Systems" (project co-PI together with Matthew Larkum and Volker Haucke). My group has moved to Berlin, and we established a lab at the Institute of Biology. Berlin’s scientific environment provided excellent settings for establishment of new networks and collaborations. Currently I am working on several projects dealing with the role of organelle and protein trafficking in synaptic plasticity, participating in teaching of bachelor and master’s courses (Experimental Biophysics and Optobiology), mentoring students and postdocs and actively involved in various scientific and administrative activities at the Humboldt University and the Charité. Taken together, this fulfils the main purpose of the Emmy Noether Program.

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