title: Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional screen.
abstract: The synaptotagmins (syts) are a family of molecules that regulate membrane fusion. There are 17 mammalian syt isoforms, most of which are expressed in the brain. However, little is known regarding the subcellular location and function of the majority of these syts in neurons, largely due to a lack of isoform-specific antibodies. Here we generated pHluorin-syt constructs harboring a luminal domain pH sensor, which reports localization, pH of organelles to which syts are targeted, and the kinetics and sites of exocytosis and endocytosis. Of interest, only syt-1 and 2 are targeted to synaptic vesicles, whereas other isoforms selectively recycle in dendrites (syt-3 and 11), axons (syt-5, 7, 10, and 17), or both axons and dendrites (syt-4, 6, 9, and 12), where they undergo exocytosis and endocytosis with distinctive kinetics. Hence most syt isoforms localize to distinct secretory organelles in both axons and dendrites and may regulate neuropeptide/neurotrophin release to modulate neuronal function.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Camin
authors.initials: C
authors.lastname: Dean
authors.forename: F Mark
authors.initials: FM
authors.lastname: Dunning
authors.forename: Huisheng
authors.initials: H
authors.lastname: Liu
authors.forename: Ewa
authors.initials: E
authors.lastname: Bomba-Warczak
authors.forename: Henrik
authors.initials: H
authors.lastname: Martens
authors.forename: Vinita
authors.initials: V
authors.lastname: Bharat
authors.forename: Saheeb
authors.initials: S
authors.lastname: Ahmed
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D049452:Green Fluorescent Proteins / Q000032:analysis; D006624:Hippocampus / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: C485187:PHluorin; D020033:Protein Isoforms; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins