title: Vesicular reuptake inhibition by a synaptotagmin I C2B domain antibody at the squid giant synapse.
abstract: Synaptotagmin (Syt) I, a ubiquitous synaptic vesicle protein, comprises a transmembrane region and two C2 domains. The C2 domains, which have been shown to be essential for both synaptic vesicle exocytosis and endocytosis, are also seen as the Ca(2+) sensors in synaptic vesicular release. In a previous study, we reported that a polyclonal antibody raised against the squid (Loligo pealei) Syt I C2B domain, while inhibiting vesicular endocytosis, was synaptic release neutral at the squid giant synapse. Recent reports concerning the C2B requirements for synaptic release prompted us to readdress the role of C2B in squid giant synapse function. Presynaptic injection of another anti-Syt I-C2B antibody (using recombinant whole C2B domain expressed in mammalian cell culture as an antigen) into the presynaptic terminal reproduced our previous results, i.e., reduction of vesicular endocytosis without affecting synaptic release. This set of results addresses the issue of the geometrical arrangement of the Ca(2+) sensor, allowing the C2B domain antibody to restrict Ca(2+)-dependent C2B self-oligomerization without modifying the Ca(2+)-dependent release process.
authors.affiliation: Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. llinar01@popmail.med.nyu.edu
authors.forename: Rodolfo R
authors.initials: RR
authors.lastname: Llinás
authors.forename: Mutsuyuki
authors.initials: M
authors.lastname: Sugimori
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Moran
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Moreira
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology*; D000918:Antibody Specificity; D001692:Biological Transport / Q000187:drug effects; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D002522:Chlorocebus aethiops; D049832:Decapodiformes / Q000502:physiology* / Q000648:ultrastructure; D004594:Electrophysiology; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: D000906:Antibodies; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050863:Synaptotagmin I; D050857:Synaptotagmins; D002118:Calcium