title: Control of synaptic vesicle endocytosis by an extracellular signalling molecule.
abstract: Signalling cascades control multiple aspects of presynaptic function. Synaptic vesicle endocytosis was assumed to be exempt from modulation, due to its essential role maintaining synaptic vesicle supply and thus neurotransmission. Here we show that brain-derived neurotrophic factor arrests the rephosphorylation of the endocytosis enzyme dynamin I via an inhibition of glycogen synthase kinase 3. This event results in a selective inhibition of activity-dependent bulk endocytosis during high-intensity firing. Furthermore, the continued presence of brain-derived neurotrophic factor alleviates the rundown of neurotransmission during high activity. Thus, synaptic strength can be modulated by extracellular signalling molecules via a direct inhibition of a synaptic vesicle endocytosis mode.
authors.affiliation: Centre for Integrative Physiology, George Square, University of Edinburgh, EH8 9XD Scotland, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Smillie
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pawson
authors.forename: Emma M
authors.initials: EM
authors.lastname: Perkins
authors.forename: Mandy
authors.initials: M
authors.lastname: Jackson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cousin
mesh_terms: D000818:Animals; D001692:Biological Transport; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D034284:Dynamin I / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002867:Chromones; D034284:Dynamin I; D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3; D009025:Morpholines; D018377:Neurotransmitter Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one