title: Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals.
abstract: Presynaptic terminals are specialized sites for information transmission where vesicles fuse with the plasma membrane and are locally recycled. Recent work has extended this classical view, with the observation that a subset of functional vesicles is dynamically shared between adjacent terminals by lateral axonal transport. Conceptually, such transport would be expected to disrupt vesicle retention around the active zone, yet terminals are characterized by a high-density vesicle cluster, suggesting that counteracting stabilizing mechanisms must operate against this tendency. The synapsins are a family of proteins that associate with synaptic vesicles and determine vesicle numbers at the terminal, but their specific function remains controversial. Here, using multiple quantitative fluorescence-based approaches and electron microscopy, we show that synapsin is instrumental for resisting vesicle dispersion and serves as a regulatory element for controlling lateral vesicle sharing between synapses. Deleting synapsin disrupts the organization of presynaptic vesicle clusters, making their boundaries hard to define. Concurrently, the fraction of vesicles amenable to transport is increased, and more vesicles are translocated to the axon. Importantly, in neurons from synapsin knock-out mice the resting and recycling pools are equally mobile. Synapsin, when present, specifically restricts the mobility of resting pool vesicles without affecting the division of vesicles between these pools. Specific expression of synapsin IIa, the sole isoform affecting synaptic depression, rescues the knock-out phenotype. Together, our results show that synapsin is pivotal for maintaining synaptic vesicle cluster integrity and that it contributes to the regulated sharing of vesicles between terminals.
authors.affiliation: Department of Physiology and Neurobiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Orenbuch
authors.forename: Lee
authors.initials: L
authors.lastname: Shalev
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marra
authors.forename: Isaac
authors.initials: I
authors.lastname: Sinai
authors.forename: Yotam
authors.initials: Y
authors.lastname: Lavy
authors.forename: Joy
authors.initials: J
authors.lastname: Kahn
authors.forename: Jemima J
authors.initials: JJ
authors.lastname: Burden
authors.forename: Kevin
authors.initials: K
authors.lastname: Staras
authors.forename: Daniel
authors.initials: D
authors.lastname: Gitler
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D036681:Fluorescence Recovery After Photobleaching; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011687:Purines / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D000077546:Roscovitine; D018709:Statistics, Nonparametric; D016704:Synapsins / Q000172:deficiency / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: C498441:Bsn protein, mouse; D018691:Excitatory Amino Acid Antagonists; C073804:FM1 43; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D011687:Purines; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D016704:Synapsins; D050988:Vesicle-Associated Membrane Protein 2; D000077546:Roscovitine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine