Synaptotagmin 1-triggered lipid signaling facilitates coupling of exo- and endocytosis
Neuron. 2023-09-01; :
DOI: 10.1016/j.neuron.2023.08.016
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Bolz S(1), Kaempf N(1), Puchkov D(1), Krauss M(1), Russo G(1), Soykan T(1), Schmied C(1), Lehmann M(1), Müller R(2), Schultz C(3), Perrais D(4), Maritzen T(5), Haucke V(6).
Author information:
(1)Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany.
(2)European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany.
(3)European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany; Department of Chemical Physiology & Biochemistry, Oregon Health & Science University (OHSU), Portland, OR 97239, USA.
(4)University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
(5)Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany; Department of Nanophysiology, University of Kaiserslautern-Landau, 67663 Kaiserslautern, Germany.
(6)Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany; Faculty of Biology, Chemistry,
Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany. Electronic address: .
Exocytosis and endocytosis are essential physiological processes and are of
prime importance for brain function. Neurotransmission depends on the
Ca2+-triggered exocytosis of synaptic vesicles (SVs). In neurons, exocytosis is
spatiotemporally coupled to the retrieval of an equal amount of membrane and SV
proteins by compensatory endocytosis. How exocytosis and endocytosis are
balanced to maintain presynaptic membrane homeostasis and, thereby, sustain
brain function is essentially unknown. We combine mouse genetics with optical
imaging to show that the SV calcium sensor Synaptotagmin 1 couples exocytic SV
fusion to the endocytic retrieval of SV membranes by promoting the local
activity-dependent formation of the signaling lipid phosphatidylinositol
4,5-bisphosphate (PI(4,5)P2) at presynaptic sites. Interference with these
mechanisms impairs PI(4,5)P2-triggered SV membrane retrieval but not exocytic SV
fusion. Our findings demonstrate that the coupling of SV exocytosis and
endocytosis involves local Synaptotagmin 1-induced lipid signaling to maintain
presynaptic membrane homeostasis in central nervous system neurons.
Copyright © 2023 Elsevier Inc. All rights reserved.
Conflict of interest statement: Declaration of interests The authors declare no
competing financial interests.