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Coupling exo- and endocytosis: An essential role for PIP2 at the synapse
Authors:Marta Koch  Matthew Holt
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
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.
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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