title: A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis.
abstract: The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles ('bulk' endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, United States Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors: Yumei
authors: Y
authors: Wu
authors: Department of MCD Biology, University of Colorado, Boulder, United States.
authors: Eileen T
authors: ET
authors: O'Toole
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Martine
authors: M
authors: Girard
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Brigitte
authors: B
authors: Ritter
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, United States Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors: Mirko
authors: M
authors: Messa
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
authors: Xinran
authors: X
authors: Liu
authors: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Peter S
authors: PS
authors: McPherson
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, United States Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States.
authors: Shawn M
authors: SM
authors: Ferguson
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, United States Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States pietro.decamilli@yale.edu.
authors: Pietro
authors: P
authors: De Camilli
mesh_terms: D000818:Animals; D002966:Clathrin / Q000172:deficiency / Q000235:genetics*; D034284:Dynamin I / Q000172:deficiency / Q000235:genetics*; D034286:Dynamin III / Q000172:deficiency / Q000235:genetics*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D002966:Clathrin; D009419:Nerve Tissue Proteins; D034284:Dynamin I; D034286:Dynamin III
keywords: endosome; exocytosis; high pressure freezing; synaptic transmission; syndapin