title: Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling.
abstract: Synaptic vesicle endocytosis is critical for maintaining synaptic communication during intense stimulation. Here we describe Tweek, a conserved protein that is required for synaptic vesicle recycling. tweek mutants show reduced FM1-43 uptake, cannot maintain release during intense stimulation, and harbor larger than normal synaptic vesicles, implicating it in vesicle recycling at the synapse. Interestingly, the levels of a fluorescent PI(4,5)P(2) reporter are reduced at tweek mutant synapses, and the probe is aberrantly localized during stimulation. In addition, various endocytic adaptors known to bind PI(4,5)P(2) are mislocalized and the defects in FM1-43 dye uptake and adaptor localization are partially suppressed by removing one copy of the phosphoinositide phosphatase synaptojanin, suggesting a role for Tweek in maintaining proper phosphoinositide levels at synapses. Our data implicate Tweek in regulating synaptic vesicle recycling via an action mediated at least in part by the regulation of PI(4,5)P(2) levels or availability at the synapse.
authors.affiliation: Department of Molecular and Human Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Patrik
authors.initials: P
authors.lastname: Verstreken
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohyama
authors.forename: Claire
authors.initials: C
authors.lastname: Haueter
authors.forename: Ron L P
authors.initials: RL
authors.lastname: Habets
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Lin
authors.forename: Laura E
authors.initials: LE
authors.lastname: Swan
authors.forename: Cindy V
authors.initials: CV
authors.lastname: Ly
authors.forename: Koen J T
authors.initials: KJ
authors.lastname: Venken
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018076:DNA, Complementary; D004175:Diptera; D029721:Drosophila Proteins / Q000502:physiology*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D005124:Eye Abnormalities / Q000235:genetics; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; C073804:FM1 43; D009419:Nerve Tissue Proteins; D018129:Phosphatidylinositol Phosphates; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds