We study the molecular and biophysical mechanisms underlying vesicle trafficking in neurons and in particular in their axons and presynaptic nerve terminals.
Membrane vesicles filled with different cargos serve for communication between cells, intracellular compartments and organelles. We study the molecular and biophysical mechanisms underlying vesicle trafficking in neurons and in particular in their axons and presynaptic nerve terminals.
Our current interest is in the molecular mechanisms, which link the synaptic vesicle cycle with autophagosome-lysosomal and protein degradation pathways.
It is known, that effector synaptic proteins and scaffolding molecules, which are involved in coordination and targeting of the effector proteins and membrane lipids, control vesicle trafficking events in the nerve terminal.
Our recent studies show that deletion of certain genes and genetic perturbations of transcription factors implicated in neurodegenerative diseases cause dramatic changes in vesicle trafficking, activation of autophagasome-lysosomal pathway in synaptic terminals and formation of pathological protein aggregates in neurons.
We are aiming at characterizing the signaling mechanisms that regulate the vesicle trafficking events and degradation pathways at synapses and clarify how do they become affected at early stages of neurodegenerative diseases in particular in Parkinson´s disease. To address our goals we use several model systems such as giant reticular spinal axon in lamprey, Drosophila neuromuscular junction and mammalian neurons, in combination with molecular biology, genetics, cellular imaging techniques, and intracellular recordings.
We believe that our studies will pave the way for identification of therapeutic targets for treatments of neurodegenerative disorders.
Our laboratory is responsible for the “Correlative light and electron microscopy unit (CLEM)”, which is specialized in guiding researchers in correlative microcopy (CLEM) and immmuno-EM technologies and helps with EM projects, including conventional and cryo-EM. It provides courses and education for researches and students wiling to perform EM-related projects and supervises the use of the equipment for correlative LM-EM available at the Department.
Intersectin associates with synapsin and regulates its nanoscale localization and function.
Gerth F, Jäpel M, Pechstein A, Kochlamazashvili G, Lehmann M, Puchkov D, et al
Proc. Natl. Acad. Sci. U.S.A. 2017 11;114(45):12057-12062
Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane.
Wen PJ, Grenklo S, Arpino G, Tan X, Liao HS, Heureaux J, et al
Nat Commun 2016 08;7():12604
Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and function via an ubiquitin- proteasome mediated mechanism.
Mitroi DN, Deutschmann AU, Raucamp M, Karunakaran I, Glebov K, Hans M, et al
Sci Rep 2016 11;6():37064
An Endocytic Scaffolding Protein together with Synapsin Regulates Synaptic Vesicle Clustering in the Drosophila Neuromuscular Junction.
Winther ÅM, Vorontsova O, Rees KA, Näreoja T, Sopova E, Jiao W, et al
J. Neurosci. 2015 Nov;35(44):14756-70
Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease.
Laguna A, Schintu N, Nobre A, Alvarsson A, Volakakis N, Jacobsen JK, et al
Nat. Neurosci. 2015 Jun;18(6):826-35