Coupling exo- and endocytosis: An essential role for PIP2 at the synapse |
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Authors: | Marta Koch Matthew Holt |
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Institution: | 1. Laboratory of Neurogenetics, VIB Center for the Biology of Disease and K.U. Leuven Center for Human Genetics, O&N4 Herestraat 49, 3000 Leuven, Belgium;2. Laboratory of Glia Biology, VIB Center for the Biology of Disease and K.U. Leuven Center for Human Genetics, O&N4 Herestraat 49, 3000 Leuven, Belgium |
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Abstract: | Chemical synapses are specialist points of contact between two neurons, where information transfer takes place. Communication occurs through the release of neurotransmitter substances from small synaptic vesicles in the presynaptic terminal, which fuse with the presynaptic plasma membrane in response to neuronal stimulation. However, as neurons in the central nervous system typically only possess ~ 200 vesicles, high levels of release would quickly lead to a depletion in the number of vesicles, as well as leading to an increase in the area of the presynaptic plasma membrane (and possible misalignment with postsynaptic structures). Hence, synaptic vesicle fusion is tightly coupled to a local recycling of synaptic vesicles. For a long time, however, the exact molecular mechanisms coupling fusion and subsequent recycling remained unclear. Recent work now indicates a unique role for the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), acting together with the vesicular protein synaptotagmin, in coupling these two processes. In this work, we review the evidence for such a mechanism and discuss both the possible advantages and disadvantages for vesicle recycling (and hence signal transduction) in the nervous system. This article is part of a Special Issue entitled Lipids and Vesicular Transport. |
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Keywords: | AP Adaptor protein Arf ADP-ribosylation factor CALM clathrin assembly lymphoid myeloid leukemia protein CAPS Calcium activated protein for secretion Cdk Cyclin-dependent kinase DAG Diacylglycerol EMS Ethyl methanesulfonate FCHo1/2 F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 GFP Green fluorescent protein GST glutathione S-transferase HIP Huntingtin interacting protein IP3 Inositol trisphosphate MARCM Mosaic analysis with a repressible cell marker NMJ Neuromuscular junction PH Pleckstrin homology PIP2 Phosphatidylinositol 4 5-bisphosphate PKC Protein kinase C PLC Phospholipase C PLD Phospholipase D PS Phosphatidylserine PX Phox RIM Rab3 interacting molecule SCAMP Secretory carrier membrane protein SHD Stonin homology domain SNARE Soluble NSF attachment protein receptor VAMP Vesicle associated membrane protein μHD mu-homology domain |
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