Subcellular Dynamics in Neurons

The Focus Group "Subcellular Dynamics in Neurons" comprises as principal investigators Hans Fischer Fellow, Prof. Melike Lakadamyali (University of Pennsylvania), Hans Fischer Senior Fellow Prof. Maya Schuldiner (The Weizmann Institute) and – as host – former Hans Fischer Tenure Track Fellow, Prof. Thomas Misgeld. Together this group explores how nerve cells manage their packed interior and establish the appropriate distribution and density of organelles in different compartments, such as axons and synapses. Neurons are extreme cells: Their processes can easily dwarf the cell bodies volume by a factor of 1:1000 – still the cell body needs to supply organelles to all parts of the cell, and organelles need to engage in specific cooperation to accomplish their tasks. Two major principles govern this process: Controlled intracellular trafficking, known as axonal transport, and establishment of specific organelle interactions, known as organellar contact sites. It appears that despite these specific adaptations to handle the challenges that come with having an extended geometry, neurons remain vulnerable - and disrupted transport or organelle function appear as sites of vulnerability in many neurological diseases. Together the focus group uses advanced imaging techniques and bioinformatics analysis based on screens in other cell types to decipher the mechanisms of organelle distribution and homeostasis in neurons.

We are currently focusing on two specific questions:

(1) How are essential organelles – specifically mitochondria, which support critical bioenergetic and metabolic functions in neurons – delivered to synapses, and how is their local ‘life cycle’ organized.

(2) How are inter-organellar contact sites that we know from non-vertebate cells – specifically those between mitochondria and peroxisomes – organized in the distal periphery of neurons? How are they assembled and maintained?

TUM-IAS funded doctoral candidate:
Antoneta Gavoci, Institute of Neuronal Cell Biology, TUM

TUM-IAS funded postdoctoral researcher:
Dr. Shabab Hannan, Institute of Neuronal Cell Biology, TUM

Focus Group-associated medical doctoral candidate:
Natalia Marahori, Institute of Neuronal Cell Biology, TUM

Publications by the Focus Group

2019

  • Fecher, Caroline; Trovò, Laura; Müller, Stephan A.; Snaidero, Nicolas; Wettmarshausen, Jennifer; Heink, Sylvia; Ortiz, Oskar; Wagner, Ingrid; Kühn, Ralf; Hartmann, Jana; Karl, Rosa Maria; Konnerth, Arthur; Korn, Thomas; Wurst, Wolfgang; Merkler, Doron; Lichtenthaler, Stefan F.; Perocchi, Fabiana; Misgeld, Thomas: Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nature Neuroscience 22 (10), 2019, 1731-1742 mehr…
  • Witte, Maarten E.; Schumacher, Adrian-Minh; Mahler, Christoph F.; Bewersdorf, Jan P.; Lehmitz, Jonas; Scheiter, Alexander; Sánchez, Paula; Williams, Philip R.; Griesbeck, Oliver; Naumann, Ronald; Misgeld, Thomas; Kerschensteiner, Martin: Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis. Neuron 101 (4), 2019, 615-624.e5 mehr…

2018

  • Colombo, Alessio; Hsia, Hung‐En; Wang, Mengzhe; Kuhn, Peer‐Hendrik; Brill, Monika S; Canevazzi, Paolo; Feederle, Regina; Taveggia, Carla; Misgeld, Thomas; Lichtenthaler, Stefan F: Non‐cell‐autonomous function of DR6 in Schwann cell proliferation. The EMBO Journal 37 (7), 2018, e97390 mehr…
  • Kiss, Alexa; Fischer, Irmgard; Kleele, Tatjana; Misgeld, Thomas; Propst, Friedrich: Neuronal Growth Cone Size-Dependent and -Independent Parameters of Microtubule Polymerization. Frontiers in Cellular Neuroscience 12, 2018 mehr…