title: Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I.
abstract: Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size control, impaired activity-dependent SV retrieval and defective synaptic activity. Detailed molecular analyses demonstrate that syndapin I plays an important role in the recruitment of all dynamin isoforms, central players in vesicle fission reactions, to the membrane. Consistently, syndapin I KO mice share phenotypes with dynamin I KO mice, whereas their seizure phenotype is very reminiscent of fitful mice expressing a mutant dynamin. Thus, syndapin I acts as pivotal membrane anchoring factor for dynamins during regeneration of SVs.
authors.affiliation: Institute of Biochemistry I, Jena University Hospital-Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Koch
authors.forename: Isabella
authors.initials: I
authors.lastname: Spiwoks-Becker
authors.forename: Victor
authors.initials: V
authors.lastname: Sabanov
authors.forename: Anne
authors.initials: A
authors.lastname: Sinning
authors.forename: Tamar
authors.initials: T
authors.lastname: Dugladze
authors.forename: Anne
authors.initials: A
authors.lastname: Stellmacher
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ahuja
authors.forename: Julia
authors.initials: J
authors.lastname: Grimm
authors.forename: Susann
authors.initials: S
authors.lastname: Schüler
authors.forename: Anke
authors.initials: A
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Angenstein
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmed
authors.forename: Alexander
authors.initials: A
authors.lastname: Diesler
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Susanne
authors.initials: S
authors.lastname: Tom Dieck
authors.forename: Rainer
authors.initials: R
authors.lastname: Spessert
authors.forename: Tobias Maria
authors.initials: TM
authors.lastname: Boeckers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Christian Andreas
authors.initials: CA
authors.lastname: Hübner
authors.forename: Detlef
authors.initials: D
authors.lastname: Balschun
authors.forename: Tengis
authors.initials: T
authors.lastname: Gloveli
authors.forename: Michael Manfred
authors.initials: MM
authors.lastname: Kessels
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D006624:Hippocampus / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000502:physiology / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology / Q000648:ultrastructure; D012640:Seizures / Q000235:genetics; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; C114726:Pacsin1 protein, mouse; D010750:Phosphoproteins; D034281:Dynamins